bluuebunny/crossref_metadata_2025 huggingface dataset:
Through-Care: The Client's Point of View
Authors: Kingston Rosaline
Published: March 2007

Through-care is a concept which has been in the probation officer's vocabulary for well over a decade now, but little has been written about how this service is perceived by its recipients. The author undertook some research into this field by interviewing 22 imprisoned clients at the beginning, middle and end of their sentences. This was followed up by interviews with their local probation officers, as well as the senior probation officers in those offices. As the research was based upon a young prisoners' centre, all of the sample were subject to statutory after-care. However, many of the conclusions are of relevance to the general policy of through-care in the Probation Service.
The May Report: a personal Comment
Authors: Hutchinson R.A.
Published: March 2007

I suppose it was all bound to be something of an anti-climax when it was finally published, but we could be excused some sense of anticipation, as anyone can when the exam results are expected. The Governor had arranged for copies of the Report to be rushed to the prison the same evening via the M1 and the AG's fast car, and the Probation Department were contem plating the possibility of redundancy within the month, following giving prison officers a crash course in social work.
Modernizing Information Training in China
Authors: Campbell Harry
Published: March 2007

China's modernisation programme places great strains on existing library resources and personnel, which are also affected by the growth of foreign literature collections, the ex pansion of Chinese publishing and the increase in the educated population. Over 30 university library science departments offer full-time courses. The training facilities available in Beij ing and Shanghai, and the activities of the new national information college at Wuhan Universi ty, Hebei Province, are described and the opportunities for foreign assistance outlined.
Information needs for rural development
Authors: Broadbent K.P.
Published: March 2007

The sixth in a series of articles on the activities of the Information Sciences Division (ISD) of the International development Research Centre (IDRC). Discusses an information strategy for the rural sector in developing countries. Traces the broad concept of rural development over five phases and examines the difficulty in providing rural populations with greater access to information aimed at improving their lives. Consideration of user needs is critical since information must be focused, generated by demand, grassroots-based, reflective of local conditions and based on indigenous knowledge. ISD's rural development approach is multidisciplinary. Projects focus on information requirements across basic social, economic and scientific issues. Rural information projects also require effective information flows at each phase to ensure that knowledge is actually being used. Recommends the strengthening and coordination of local information systems to better support rural populations as well as decision-makers.
Rehabilitating an agricultural library in Mozambique
Authors: Naber Gerrit
Published: March 2007

Describes the process of rehabilitation of the library of the Faculty of Agronomy, Eduardo Mondlane University, Maputo, Mozambique.
Equipment for information work in developing countries
Authors: Yapa N.U.
Published: March 2007

Libraries use various types of equipment for information handling to improve the speed, accuracy and quality of work and reduce the cost and effort involved. Instead of purchasing equipment, it may be hired or leased, or bureau services used. Outlines the facilities which libraries require to be able to use equipment effectively. Identifies four basic types of equipment: electronic data processing; reprographic; audiovisual; and binding. Discusses problems associated with the use of equipment by libraries in developing countries. Describes the centralized equipment facilities at the Sri Lanka Scientific and Technical Information Centre (SLSTIC), which provides services to other libraries in Sri Lanka.
Developing an agricultural database in Malawi
Authors: Ngwira Margaret
Published: March 2007

Describes the processes of eliciting donor support in order to acquire microcomputer capacity in the Faculty of Agriculture Library, University of Malawi, and the successful development of a computerized database using Mini-micro CDS/ISIS software.
A National Information Documentation Centre for Nigeria: some practical considerations
Authors: Nweke Ken M. C.
Published: March 2007

The need for coordination of national information documentation in Nigeria has been recognized and extensively discussed among librarians and information professionals throughout the country for over two decades. However, there is a need to avoid duplication and wastage of essential resources by establishing a National Information Documentation Centre (NIDOC) that would complement the effort of the National Library by emphasizing areas of greater national need in its coverage. Relevant functions of the National Library are examined and weaknesses in achieving set objectives identified. It is recommended that the proposed NIDOC be initially located at the National Library to utilize its three decades of experience in national documentation.
Lorazepam in the elderly—a retrospective study of the side-effects in 20 patients
Authors: Ancill R.J. , Embury G.D. , MacEwan G.W. , Kennedy J.S.
Published: March 2007

In a retrospective study of 20 elderly patients who were prescribed lorazepam prior to their admission to a geriatric psychiatry inpatient unit, the average length of prescription of the drug was 18 weeks with inadequate follow-up. Side-effects were common and consisted of oversedation, amnestic disorders, confusion, depression and ataxia. The majority of such events resolved on withdrawal of lorazepam in hospital. Particular note is made of the pro duction of a drug-induced pseudodementia misdiagnosed as a 'true' dementia which again resolved on cessation of the drug. It is concluded that there are insufficient data to recommend lorazepam over any other agent in the elderly and care should always be exercised when prescribing in older patients.
Pharmacological characterization in the rat of grooming and other behavioural responses to the D1 dopamine receptor agonist R-SK&F 38393
Authors: Molloy Anthony G. , Waddington John L.
Published: March 2007

Grooming, sniffing, Iocomotor and rearing responses to the D1 dopamine receptor agonist SK&F 38393, as the racemic compound or its R-enantiomer, were characterized pharmacologically using typical neuroleptics, non-dopaminergic antagonists, selective D1 antagonists and selective D2 antagonists. The typical neuroleptics haloperidol and flupenthixol blocked all behaviours induced by SK&F 38393; this action of flupenthixol was stereoselective for its cis(Z)-isomer but not its trans(E)-isomer. Non-dopaminergic antagonists failed to reproduce the consistent effects of typical neuroleptics. The selective D1 antagonist SCH 23390 potently blocked all responses to SK&F 38393. A related selective D1 antagonist, SK&F 83566, also blocked these responses, and this action was stereoselective for its R-enantiomer but not its S-enantiomer. These data suggest that D1 receptor stimulation is the primary mechanism underlaying the induction of these behaviours by SK&F 38393. However, the expression of certain individual responses to SK&F 38393 were sensitive to attenuation by the selective D2 antagonists sulpiride or metoclopramide. These results extend the emerging view that the D1 receptor is behaviourally relevant and that there exist functional interactions between D1 and D2 receptor systems in the regulation of behaviour.
Relationship between extrapyramidal symptoms and serum anticholinergic levels in treated chronic schizophrenics
Authors: Bamrah J.S. , Krska Janet , Soni Som D.
Published: March 2007

Serum anticholinergic levels were measured by radioreceptor assay (RRA) in schizophrenic patients treated for drug-induced Parkinsonism; 68 patients stabilized on a single neuroleptic and an anticholinergic antiparkinsonian agent (benzhexol, benztropine or procyclidine) were assessed using the extrapyramidal side effects (EPS) scale prior to each blood sampling. Serum anticholinergic levels showed a significant inverse correlation with EPS but did not appear to be dose-related in any of the three anticholinergic drug groups. Percentage binding to proteins was significantly less with benztropine than either benzhexol or procyclidine. Serum-free anticholinergic levels correlated significantly with total serum levels in the benzhexol and procyclidine groups but not in the benztropine group. At serum levels above 4.5 pmol/ml atropine equivalents, EPS was significantly less than at levels below that. We discuss the implications of this finding and suggest practical clinical applications of measurement of serum anticholinergic levels. Serum neuroleptic and serum prolactin levels did not correlate with either dose or serum level of anticholinergics.
Serum haloperidol levels and clinical response in chronic, treatment-resistant schizophrenic patients
Authors: Browne F.W.A. , Cooper S.J. , Wilson R. , King D.J.
Published: March 2007

Eleven chronic treatment-resistant schizophrenic in-patients were treated with haloperidol (HPL) or placebo with a fixed ascending dose schedule for 20 weeks. Seven patients relapsed and were withdrawn and five of these re-entered, single-blind, on known active treatment. Two weekly clinical ratings and weekly serum HPL levels were carried out throughout the study. More patients on placebo dropped out and at an earlier stage than those on active treatment but the difference was not statistically significant. Despite wide individual variations in both serum HPL levels and clinical response, these were positively correlated. HPL appeared to be of more value in the prevention of relapse than in symptom reduction. Overall, the clinical response was poor and a 'therapeutic window' could not be demonstrated either for the group as a whole or in any individual patient. There was no additional therapeutic benefit in exceeding serum HPL levels of 20 ng/ml in any of our patients. Since this serum level was achieved by daily doses of 10-40 mg HPL and the relationship between dose and serum level is linear, the use of serum HPL estimations is not likely to be of value in the routine clinical management of treatment-resistant patients.
The scopolamine model of dementia: chronic transdermal administration
Authors: Brazell C. , Preston G.C. , Ward C. , Lines C.R. , Traub M.
Published: March 2007

The transient impairments of memory produced by the muscarinic antagonist scopolamine have been adopted as a pharmacological model of Alzheimer-type dementia in normal volunteers. In this study we examined the effects of chronic (72 h) transdermal administration of scopolamine on memory, attention, sedation and visual function. The transdermal patches provided constant plasma levels of scopolamine for the duration of the study. Indices of the peripheral effects of scopolamine (visual near-point and pupil size) showed impairments that were sustained for 3 days. However, measures of sedation and memory revealed impairments that were maximal the day after patch application and which were no longer present 3 days after application. This pattern of results is discussed in relation to pharmacological modelling of Alzheimer's disease.
Temporal factors in drug discrimination: Experiments with nicotine
Authors: Stolerman I.P. , Garcha H.S.
Published: March 2007

The role of the presession interval (PI) in drug discrimination research has been studied in rats trained to discriminate nicotine from saline in a two-bar operant conditioning procedure. Different groups of rats were trained at different Pls, varying between 5 and 35 min, and tests were then carried out for qualitative and quantitative differences between the cues. There was complete generalization from nicotine cues trained at one time to tests carried out at other times. The sensitivity of the cues at different Pls to the nicotinic antagonist mecamylamine was very similar. Generalization to amphetamine was nearly complete when the nicotine cue was established with PI of 20-35 min and only partial when the PI for the nicotine was 5 min. Thus, there was no clear evidence for any qualitative difference between nicotine cues established with different PIs. However, the PI influenced quantitative aspects of the nicotine cue in a marked and complex manner. Increasing the PI during training produced a two- to three-fold decrease in the ED50, whereas increasing the PI during testing produced a two- to three-fold increase in the ED50. This shows that the effects of changing the PIs during training and testing were similar in magnitude but opposite in direction. These changes in ED50 values can be explained by pharmacokinetic considerations in conjunction with knowledge of the role of training dose in the discrimination of nicotine. The quantitative sensitivity of the drug discrimination procedure can be substantially influenced by the choice of temporal parameters used in training and testing.
Psychoneuroimmunology: An area of interest for the psychopharmacologist?
Authors: Leonard B.E.
Published: March 2007

Anecdotal evidence suggesting a causal relationship between psychiatric illness, environmental stress and a malfunctioning immune system goes back to antiquity. Recently, clinical and experimental studies have established the interrelationship between neuro- endocrine regulation, the immune system and abnormalities in central neurotransmission which may be deranged as a consequence of stressful events. This short review is an attempt to assess the evidence implicating altered immune responsiveness in depression and to consider the impact of different types of environmental stress in triggering the immune malfunction. While these findings are of considerable biological importance, it is presently unclear whether the immunological changes are primary or secondary to the disease states.
Biphasic effects of propranolol on a temporal generalization gradient in the rat
Authors: Terry Philip , Salmon Peter
Published: March 2007

Rats were trained on a fixed interval (FI 20 s) schedule of food reinforcement, then subjected to drug trials on an ABBA design. Responses, recorded in 2 s post-reinforcement bins, formed a temporal generalization gradient. d,l-propranolol (7.5 mg/kg, intraperitoneally) decreased responding in bins two to four, in which control response rates were relatively low, but increased responding in bins five to eight, in which control response rates were higher. The effect was weaker at 5 mg/kg, non-significant at 2.5 mg/kg and absent at 1 and 10 mg/ kg. A similar effect was seen in a single trial of d,l-propranolol (7.5 mg/kg) on FI 40. I- propranolol (3.75 mg/kg) reproduced this effect in part, whereas d-propranolol (7.5 mg/kg) and the peripherally acting beta-blocker, atenolol (10, 20 mg/kg), were without any effect.
Object-name selection in psychiatric patients before and after neuroleptic therapy
Authors: Calvert J.E. , Babiker I.E. , Harris J.P. , Phillipson O.T. , Ford M.F. , Antebi D.L.
Published: March 2007

An object-name selection test was administered to 16 newly admitted schizo phrenic, non-schizophrenic psychotic and non-psychotic patients on admission when they were drug-free, and again 4-6 weeks later, following treatment with neuroleptics. Sixteen healthy, drug-free age-matched and sex-matched controls were similarly tested on two occasions 4-6 weeks apart. Schizophrenic and non-schizophrenic psychotic subjects made significantly more association-type errors than non-psychotic subjects and controls. A signifi cant reduction in association-type errors which was observed in both psychotic patient groups on the second testing occasion may be attributed to medication. The data suggest that overinclusive thinking, as measured by the object-name selection test, is a feature of both schizophrenic and non-schizophrenic psychosis. It is concluded that tests of overinclusion are therefore of limited diagnostic utility although they may be of value in monitoring response to treatment.
Pharmacokinetics and antipsychotic effect of remoxipride in chronic schizophrenic patients
Authors: King D.J. , Devaney N. , Cooper S.J. , Blomqvist M. , Mitchell M.J.
Published: March 2007

Single dose pharmacokinetics and the antipsychotic effect of 4 weeks treatment with three fixed dose levels of remoxipride (a selective D2 receptor antagonist) were studied in chronic, stable schizophrenic inpatients. After a placebo washout of 1 month, 15 patients entered the study. Of these, 11 patients received a single 50 mg oral dose of remoxipride for pharmacokinetic evaluations. All 15 patients were randomly assigned to treatment with oral remoxipride either 25 mg t.i.d., 50 mg t.i.d. or 100 mg t.i.d. for 4 weeks. Blood samples for remoxipride and prolactin assays were taken at 0, 0.33, 0.5, 0.66, 1.0, 1.5, 2, 3, 4, 8, 12, 24, 28, 32 and 48 h after drug intake. The pharmacokinetic characteristics were similar to those previously found in normal healthy volunteers: the mean peak plasma concentration of remoxipride after 50 mg was 3.3 μmol/l, the mean time to reach this was 2.1 h; the mean area under the plasma concentration/time curve was 27.8 μmol/1.h.1 -1 and the mean elimination half-life of remoxipride was 5.5 h. A significant increase in prolactin levels was detected 2 h after administration of remoxipride but they had reverted to normal 8 h after drug intake in all but one patient. Antipsychotic effects were estimated using the brief psychiatric rating scale (BPRS) and the Krawiecka rating scale (KRS) at admission, baseline (end of the 4 week placebo washout period) and after 7, 14 and 28 days treatment. Following an increase in mean psychosis ratings for both positive and negative symptoms during the placebo washout period, these decreased during active treatment and at the end of the study were similar to the scores on admission. Thus the possible efficacy of remoxipride in chronic patients with negative symptoms should be further explored in placebo controlled studies. Remoxipride was well tolerated. Sleep disorders occurred in three patients, extrapyramidal symptoms were not aggravated and no clinically significant effects were observed on the cardiovascular system, in clinical chemistry or haematology.
The dark before the dawn
Authors: Rollin Henry R.
Published: March 2007

Allow me to congratulate whoever was responsible for devising the title of this meeting. The inspired inclusion of 'The Dawn' conjures up so many poetic images and metaphors. But the one which, to my mind, is the most appropriate in the context of what the meeting is all about, is that written by Thomas Fuller, a seventeenth-century cleric and man of letters and, incidentally, a graduate of this great university (Cambridge). In his 'PISGAN- sight of Palestine' he opined, 'It is always darkest just before the day dawneth'. These words have a particular relevance for me and for those embryo psychiatrists of my generation who, before the outbreak of the Second World War, groped their therapeutic way towards the light.
Repeated treatment with antidepressant drugs and/or electroconvulsive shock (ECS) does not affect the quinpirole-induced elevation of the serum corticosterone concentration in rats
Authors: Przegalinski E. , Budziszewska B. , Blaszczynska E.
Published: March 2007

The selective dopamine D2 receptor agonist quinpirole (0.03-1 mg/kg intra peritoneally) increased dose-dependently the serum corticosterone level in rats. The effect of the maximum dose of quinpirole (0.3 mg/kg intraperitoneally) was antagonized in a dose- dependent manner by the selective D2 receptor antagonist sulpiride (3-30 mg/kg intra peritoneally), but not by the selective D1 receptor antagonist SCH-23390 (3 mg/kg intra peritoneally). Imipramine and amitriptyline (10 mg/kg per os), administered acutely or repeatedly (twice daily for 14 days), did not affect the corticosterone response to quinpirole (0.1 mg/kg intraperitoneally). The response was modified neither in animals treated repeatedly with electroconvulsive shock (ECS) (seven shocks every 2 days), nor after their combined repeated treatment with imipramine and ECS. The above results indicate that repeated treatment with antidepressant drugs and/or ECS does not affect the sensitivity of dopamine D2 receptors involved in the corticosterone response to quinpirole.
Quantitative trait loci and psychopharmacology
Authors: Plomin Robert , McClearn Gerald E. , Gora-Maslak Grazyna
Published: March 2007

Unlike simple Mendelian characteristics, individual differences in behavior, including behavioral responses to drugs, are generally distributed continuously, show substantial non-genetic as well as genetic influence, and appear to be influenced by many genes rather than one or two major genes. For these reasons, application of techniques of molecular biology to identify DNA sequences responsible for behavioral variation requires strategies that can detect genes that account for small amounts of variation, so-called quantitative trait loci (QTL). One such strategy involves analyses of association using recombinant inbred (RI) strains of mice. The RI QTL approach is especially valuable when researchers use the same RI series, such as BXD, which has 26 strains and more than 300 mapped genetic markers. Even when the progenitor inbred strains do not differ and when the strain distribution pattern of the RI strains is continuous, the approach can be used to identify and map QTL and estimate the extent to which the QTL account for genetic variance for a particular phenotype. A multivariate extension of this approach can assess genetic correlations among measures as well as the QTL underpinnings of these genetic correlations. The cumulative and integrative nature of such a program of research is the major benefit of the RI QTL approach for molecular genetic analysis of psychopharmacological processes, their physiological infrastructure, and their interface with other biological and behavioural systems.
Quantitative trait loci and psychopharmacology: response to commentaries
Authors: Plomin Robert , McClearn Gerald E. , Gora-Maslak Grazyna
Published: March 2007

The theme of our article was that a merger is needed between quantitative genetic and molecular genetic approaches in order to detect genes associated with psychopharmacological processes even when the genes account for small amounts of variance, so-called quantitative trait loci (QTL). The recombinant inbred (RI) QTL approach using the BXD RI series was discussed as a promising approach.

The commentaries by Crabbe and by McGuffin and Buckland make several excellent points to which we have little to add. Goldman and Katz, on the other hand, disagree with some of our arguments and for this reason much of the limited space of our response to the commentaries is directed towards the commentary by Goldman and Katz. We focus on three general issues that they raise: the relationship between quantitative genetics and molecular genetics (single genes vs multiple genes), reverse genetics (anonymous markers) vs forward genetics (candidate genes) and heterogeneity (narrow vs broad assessment). Our response to Goldman and Katz is that these are false dichotomies—we do not need to choose sides between major- and multiple- gene approaches, reverse and forward genetics, or narrow and broad assessment. Rather than choosing sides, we should encourage the deployment of multiple research strategies in order to maximize the probability of identifying genes that affect behavior. A major strength of the RI QTL approach is that it can identify both major- and multiple-gene effects, it employs both reverse and forward genetics, and it can be applied to both narrow and broad assessment (and its multivariate extension is ideally suited to understanding the genetic interrelationships among different levels of assessment).

After discussing these general issues raised by Goldman and Katz, we address two specific issues raised in the commentaries: multivariate analysis of multiple markers and the use of F1 crosses between RI strains to increase power. We end by mentioning the establishment of an RI QTL collaborative registry which aims to facilitate RI QTL analyses.
The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications
Authors: Swerdlow N.R. , Caine S.B. , Braff D.L. , Geyer M.A.
Published: March 2007

The startle reflex is a contraction of the skeletal and facial musculature in response to an intense sensory stimulus. While the 'primary' neural control of startle involves brain structures at, or below, the level of the mesencephalon, the startle reflex (SR) exhibits several forms of plasticity that are modulated by the forebrain. Sensorimotor gating of the SR occurs when the reflex is inhibited by a weak 'pre-pulse' that occurs 30-500 ms prior to the startling stimulus. Since 'pre-pulse inhibition' (PPI) of startle may be impaired in certain psychiatric and neurologic disorders (e.g. schizophrenia, schizotypal personality disorder and Huntington's disease), there has been considerable interest in determining the neural substrates of this form of startle plasticity. In rats, PPI is modulated by neural elements linking the limbic cortex with the striatum and pallidum. These substrates may include hippocampal glutamate efferents to the ventral striatum and striatal GABAergic efferents to the ventral pallidum. The striatal dopaminergic modulation of PPI appears to involve primarily D2, but not D1, receptors. Pallidal efferents may impinge directly on the 'primary' startle circuitry via projections to the mesencephalon or, indirectly, via projections to the thalamus. Evidence is reviewed for other neurochemical substrates of PPI—including acetylcholine and opiates. Sensorimotor gating of the startle reflex appears to have a discrete and identifiable set of neural substrates that may be important for our understanding of neuropsychiatric disorders characterized by deficient suppression or 'gating' of sensory, cognitive or motor processes.
Measuring the side effects of psychotropics: the behavioural toxicity of antidepressants
Authors: Hindmarch I. , Alford C. , Barwell F. , Kerr J.S.
Published: March 2007

The psychopharmacological profiles of 15 psychotropic drugs used as antidepressants are reviewed, and their relative behavioural toxicity ratings are compared. The pharmacodynamic activity of these drugs was assessed using a standardized test battery which included critical flicker fusion threshold (CFF), choice reaction time (CRT), tracking and subjective rating scales. It is reported that there is a wide range of behavioural toxicity exhibited by these compounds, although there is little measurable difference in their clinical efficacy. Drugs which have low behavioural toxicity should therefore be preferred as they are less disruptive of patients' everyday activities, produce better quality of life and are not counter-therapeutic.
The ratio of plasma phenylalanine to other large neutral amino acids is not a risk factor for tardive dyskinesia
Authors: Geddes John , Reynolds Gavin , Rattenbury J.M. , Peet Malcolm
Published: March 2007

The ratio of the plasma concentration of phenylalanine (PA) to the sum of the plasma concentrations of other large neutral amino acids (LNAA) was calculated in 26 chronic, in-patient schizophrenics who met diagnostic criteria for tardive dyskinesia and 22 patients who did not. No difference in the PA/LNAA ratio was found between the two groups. Small positive correlations were found between age and both PA/LNAA ratio and tardive dyskinesia. Neuroleptic dose correlated negatively with both age and plasma PA/LNAA ratio. No support was found for previous reports of increased plasma PA/LNAA ratio in schizophrenic patients with tardive dyskinesia.
Smithkline Beecham Prize for Young Psychopharmacologists
Authors: Silverstone Peter H. , Grahame-Smith David G.
Published: March 2007

The symptoms and etiology of most major psychiatric disorders probably represent an underlying disturbance of neurotransmitter function. Understanding the mechanisms which control neurotransmitter function, and in particular neurotransmitter release, is therefore of considerable importance in determining the appropriate pharmacological treatment for these disorders. Calcium entry into neurons triggers the release of a wide range of neurotransmitters and recently our understanding of the mechanisms which control neuronal calcium entry has increased considerably. Neuronal calcium entry occurs through either voltage-sensitive or receptor-operated calcium channels. This article reviews the different subtypes of calcium channel, with particular reference to their structure; drugs which act upon them; and the possible function of the subtypes identified to date. In addition, it reviews the potential role of calcium channel antagonists in the treatment of a wide range of psychiatric disorders, and concludes that these drugs may have an increasing therapeutic role particularly in the treatment of drug dependence, mood disorders and Alzheimer's disease.
Scopolamine, cognition and dementia
Authors: Parrott Andy
Published: March 2007

This symposium of the British Psychological Society Annual Conference was convened by Dr Andy Parrott (Department of Psychology, University of East London) and Dr Ian Deary (Department of Psychology, University of Edinburgh). The conference was held in Scarborough at the International Spa Complex in April 1992.
Modulatory role of D-1 and D-2 dopamine receptor subtypes in nociception in mice
Authors: Verma Anita , Kulkarni Shrinivas K.
Published: March 2007

The role of D-1 and D-2 dopamine (DA) receptors in nociception in naive as well as reserpinized mice and the modulation of the nociceptive action of morphine or naloxone by the selective D-1 and D-2 DA agonists, was investigated in mice. The D-2 DA agonists, B-HT 920 and bromocriptine produced an anti-nociceptive effect in naive mice and reversed the hyperalgesic effect of reserpine (2 mg/kg, 4 h prior) pre-treatment. The D-1 DA agonist, SKF 38393 (5 mg/kg) failed to alter the nociceptive responsiveness of naive and reserpinized mice. Apomorphine, a mixed D-1/D-2 DA agonist, produced significant analgesia in naive mice and also reversed reserpine-induced hyperalgesia. SKF 38393 (5 mg/kg) enhanced the anti-nociceptive effect of B-HT 920 (0.1 mg/kg) in naive and reserpine-pre-treated mice. The anti-nociceptive response of morphine (5 mg/kg) was enhanced by B-HT 920 while SKF 38393 reduced the same. Apomorphine (0.5 mg/kg) or the combination of B-HT 920 (0.1 mg/kg) and SKF 38393 (5 mg/kg) failed to enhance the anti-nociceptive effect of morphine. Reserpine (2 mg/kg, 4 h prior) pre-treatment significantly reduced the anti-nociceptive effect of morphine. Similarly, the hyperalgesic action of naloxone (20 mg/kg) was reversed by B-HT 920, bromocriptine and apomorphine but not by SKF 38393. The reversal of the hyperalgesic action of naloxone by B-HT 920 was blocked by pre-treatment with haloperidol (0.5 mg/kg) and sulpiride (100 mg/kg). SKF 38393 (5 mg/kg) failed to potentiate the reversal action of B-HT 920 against naloxone. These data suggest a predominant role of D-2 DA receptors in anti-nociception and the possibility of the existence of an interlink between the DAergic and opioid systems.
Effect of chronic treatment with NNC 756, a new D-1 receptor antagonist, or raclopride, a D-2 receptor antagonist, in drug-naive Cebus monkeys: dystonia, dyskinesia and D-1/D-2 supersensitivity
Authors: Gerlach Jes , Hansen Lars
Published: March 2007

When given subcutaneously in gradually increasing doses, up to 1 mg/kg, NNC 756, a dopamine (DA) D-1 antagonist, failed to produce dystonia in eight drug-naive Cebus monkeys. In contrast, raclopride, a DA D-2 antagonist, produced dystonia at low doses (0.010-0.015 mg/kg). Following pre-treatment with raclopride, NNC 756 also induced dystonia at low doses (0.015-0.025 mg/kg), but continued treatment caused tolerance, and increasing doses of NNC 756 could be administered without induction of dystonia. NNC 756 induced a dose-dependent parkinsonism (slow, stiff movements and tremor), and more sedation than raclopride. After treatment for 14 weeks, withdrawal of raclopride (0.01 mg/kg) led to mild oral dyskinesia (tardive dyskinesia), while withdrawal of NNC 756 (1.0 mg/kg) led to a special grooming syndrome, but no dyskinesia. Withdrawal of raclopride as well as NNC 756 led to behavioural D-1 and D-2 dopamine supersensitivity in the form of increased dyskinesia (including grooming after NNC 756) induced by D-1 agonist (SKF 81297) and increased arousal induced by D-2 agonist (quinpirole). These results indicate that D-1 antagonists such as NNC 756 elicit fewer extrapyramidal symptoms (both acute and tardive) than D-2 antagonists such as raclopride, although extremely high doses may cause a special grooming withdrawal syndrome.
The compliance with antidepressants in general practice
Authors: Maddox J.C. , Levi M. , Thompson C.
Published: March 2007

It has been known for some time that the compliance with antidepressants in general practice is sub-optimal, but no new studies have been carried out since the 1970s, since which time training in general practice has improved and new classes of antidepressants have been introduced. In this study 46 patients commenced on an antidepressant for clinical reasons by their GP were interviewed 10-12 weeks later by a research worker. Thirty two percent of patients stopped medication within 6 weeks and 63% of these did not inform their GP of their decision. Side-effect burden was significantly associated with non-compliance. Selective serotonin re-uptake inhibitors showed a slight but non-significant compliance advantage in this small study but all patients treated with SSRIs were initially prescribed a dose for which there is evidence of superiority of effect over placebo, while only 30% of those on tricyclics were prescribed such a dose. Further work to establish accurate methods of determining compliance and effective ways of enhancing compliance with antidepressants in general practice is required.
Serotonergic drug effects on a delayed conditional discrimination task in the rat; involvement of the 5-HT1A receptor in working memory
Authors: Herremans Arnoud H. J. , Hijzen Theo H. , Olivier Berend , Slangen Jef L.
Published: March 2007

We investigated the effects of serotonergic drugs on working memory (WM) in a delayed conditional discrimination task. The 5-HT1A receptor full agonist flesinoxan (0.3-3.0 mg/kg) dose- and delay-dependently impaired performance, indicating a specific effect on WM. The 5-HT1A receptor partial agonist ipsapirone, the 5-HT 1B/1D/2C agonist TFMPP, the 5-HT1A antagonist NAN190 and the serotonin re-uptake inhibitor fluvoxamine dose-dependently impaired performance, in a delay-independent manner, indicating no specific effect on WM. The 5-HT 2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ondansetron did not affect performance. It is suggested that the role of central serotonin receptors in WM may be restricted to 5-HT1A receptors.
Anxiogenic activity of intraventricularly administered bradykinin in rats
Authors: Bhattacharya Salil K. , Mohan Rao Patchala J. R. , Sen Ananda P.
Published: March 2007

The anxiogenic action of bradykinin was investigated in rats and compared with that of yohimbine, a known anxiogenic agent. Bradykinin (0.5, 1 and 2 μg/rat) was administered intracerebroventricularly (i.c.v.), whereas yohimbine (2 mg/kg) was administered i.p. The experimental methods used were the open- field, elevated plus-maze, social interaction and novelty suppressed feeding latency tests, and estimation of brain tribulin activity in terms of endogenous monoamine oxidase (MAO) A and MAO B inhibition. The behavioural and biochemical effects induced by bradykinin were qualitatively similar to those of yohimbine. Thus, both the drugs reduced ambulation and rears, and increased immobility and defecation, in the open-field test. They decreased the number of entries and time spent on the open arms of the elevated plus-maze, reduced social interaction in paired rats and increased the feeding latency in an unfamiliar environment in 48 h food-deprived rats. These effects are known to be associated with anxiety in animals. Bradykinin and yohimbine increased rat brain tribulin activity, the effect on the MAO A inhibitor component being more marked than that on the MAO B inhibitor component. The MAO A inhibitor component has been postulated to be the major anxiogenic moiety of tribulin. Lorazepam, a well known benzodiazepine anxiolytic agent, attenuated the anxiogenic effects of bradykinin and yohimbine, which may not be a functional effect. The investigation indicates that, like cholecystokinin (CCK), bradykinin may function as an endogenous anxiogenic peptide.
Epinephrine and fear of bodily sensations in panic disorder and social phobia
Authors: Veltman Dirk J. , van Zijderveld Gudo , Tilders Fred J H. , van Dyck Richard
Published: March 2007

Fear of bodily symptoms of arousal has been implicated in the pathogenesis of both spontaneously occurring and experimentally provoked panic. Fear of bodily symptoms may be characteristic for panic disorder (PD) and is hypothesized to predict state anxiety and panic frequency during experimentally induced peripheral arousal. Twenty-eight subjects, 14 with PD and 14 with social phobia (SP) were infused with placebo and epinephrine (20, 40 and 80 ng/kg bodyweight/min) according to a fixed schedule in a single blind design. Fear of bodily symptoms was higher in subjects with PD, who also reported more bodily symptoms and higher state anxiety scores during the experiment. The panic rate (five out of 14), however, was the same in both groups. Panickers did not differ from non-panickers in trait- or baseline measures except for fear of bodily symptoms, which was marginally higher in panickers. Panickers showed greater reactivity in heart rate, diastolic blood pressure and capillary PCO2. Our data do not support the hypothesis of a major role for fear of bodily symptoms in epinephrine-induced panic. Also, our results do not demonstrate a different reaction to epinephrine in PD and SP with situational panic attacks.
Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone
Authors: Motzo C. , Porceddu M.L. , Maira G. , Flore G. , Concas A. , Dazzi L. , Biggio G.
Published: March 2007

The neurosteroid allopregnanolone is a potent and efficacious modulator of γ-aminobutyric acid (GABA) type A receptors. The effects of intracerebroventricular injection of allopregnanolone (5 to 15 μg in 5 μl) on basal and stress-induced changes in the extracellular concentrations of dopamine were investigated by microdialysis in various brain areas of freely moving rats and compared with those of the benzodiazepine midazolam (1 to 10 μg in 5 μl). Allopregnanolone reduced (by a maximum of 65 to 75%) basal dopamine content in the prefrontal cortex and nucleus accumbens in a dose-dependent manner, but had no effect on dopamine output in the striatum. Allopregnanolone (10 to 15 μg) also completely prevented the increase in extracellular dopamine concentrations in the nucleus accumbens and cerebral cortex induced by foot-shock stress. Midazolam reduced basal dopamine content in all three brain regions studied as well as the stress- induced increase in dopamine content in the nucleus accumbens and cerebral cortex with a greater potency than allopregnanolone. These results suggest that endogenous neurosteroids may participate in the GABAergic modulation of dopaminergic transmission in the rat cerebral cortex and nucleus accumbens, two brain areas which are important in the regulation of emotional processes. These agents do not appear to affect striatal dopaminergic transmission which modulates motor function.
Risperidone in the treatment of Tourette syndrome: a retrospective case note study
Authors: Robertson Mary M. , Scull David A. , Eapen Valsamma , Trimble Michael R.
Published: March 2007

Nineteen patients with Tourette syndrome (TS) were treated with risperidone, at a mean daily dose of 1.5 mg. Of those, 41% responded positively, 35% felt that it had made no difference, while it made 24% worse. Although 53% of the patients experienced side-effects, none had extrapyramidal side-effects. At follow-up, 8 to 11 months later, only two of 19 (11 %) patients were still taking risperidone. We suggest that risperidone does have a role in a minority of TS sufferers but it is not suggested as the first line treatment. More placebo-controlled studies using risperidone are clearly indicated.
The stimulus properties of two common over-the-counter drug mixtures: dextromethorphan + ephedrine and dextromethorphan + diphenhydramine
Authors: Gauvin D.V. , Vanecek S.A. , Baird T.J. , Vallett M. , Briscoe R.J. , Carl K.L. , Holloway F.A. , Sannerud C.A.
Published: March 2007

Two groups of rats were trained in a two-choice drug discrimination procedure under a fixed-ratio 10 schedule of food reinforcement. One group of rats ( n=12) was trained to discriminate the presence and absence of a drug mixture containing 10 mg/kg dextromethorphan + 10 mg/kg diphenhydramine. The other group of rats ( n=12) was trained to discriminate the presence and absence of another drug mixture containing 10 mg/kg dextromethorphan + 10 mg/kg ephedrine. Cross-generalization tests conducted with each of the stimulus elements demonstrated that (1) the drug mixtures were not perceived as new entities distinct from their component elements and (2) the stimulus element saliency may be a factor determining the nature of discriminative control by drug mixtures. Cross-generalization tests conducted with the psychomotor stimulants, cocaine and amphetamine, engendered complete generalization to the training cues in both groups, whereas, pentobarbital engendered predominantly saline- or default-lever responding. These data suggest a potential abuse liability for both of these common over-the-counter drug mixtures and cautions against the use of such combinations in pediatric patients.
Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users
Authors: Bernik M.A. , Gorenstein C. , Vieira Filho A.H.G.
Published: March 2007

The acute effects of flumazenil, a benzodiazepine (BZD) receptor antagonist in long-term BZD users were used as a possible test to detect physiological dependence. Thirty-four subjects (20 females, 14 males) aged 26-48 years (mean ± SD, 42.4 ± 8.5 years), all chronic users of low doses of diazepam (5-20 mg/day,14.2 ± 4.8 mg/day) for 5 to 28 years (10.5 ± 6 years), received a single 1-mg i.v. flumazenil dose or saline, infused slowly under double-blind conditions. Physiological dependence was suggested as all patients receiving flumazenil developed an anxiety reaction while the placebo group did not. Flumazenil triggered a qualitatively different reaction amounting to a panic attack during infusion in nine out of 15 patients. These patients had a diagnosis of panic disorder or a history of panic attacks. Caution should be exercised when giving flumazenil to panic patients who are taking BZDs as maintenance treatment.
Comparison of effects of a range of 5 -HT receptor modulators on consumption and preference for a sweetened ethanol solution in rats
Authors: Silvestre Jordi S. , Palacios José M. , Fernandez Andres G. , O'Neill Michael F.
Published: March 2007

This study assessed the effects of a range of serotonergic agents on preference for a slightly sweetened ethanol solution (10% ethanol, 3% glucose) in rats. A two-bottle, free-choice paradigm was used following induction of ethanol consumption. The model used provides a robust and reliable level of ethanol self-administration in normal laboratory rats. Ethanol consumption was significantly and selectively reduced by the 5- hydroxytryptamine-1A (5-HT1A) full agonist 8-OH-DPAT (0.3-1.0 mg/kg) and the 5-HT 3 antagonist granisetron (0.1-1.0 mg/kg). Non-specific reductions in fluid consumption were induced by the 5-HT1B agonist RU 24969 (0.1- 1.0 mg /kg) and the 5-HT2 antagonist ritanserin (1.0-6.0 mg/kg). These studies thus confirm the potential for decreasing ethanol consumption and ethanol preference of 5-HT 1A agonists and 5-HT3 antagonists, but failed to find any selective effects for agents acting at 5-HT1B or 5-HT2 receptors.
Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls
Authors: Abel Kathryn , Waikar Manoj , Pedro Brenda , Hemsley David , Geyer Mark
Published: March 2007

The aim of this study was to examine the effect of repeated testing on prepulse inhibition (PPI) and habituation of the startle reflex. Fifteen healthy control subjects (eight males, mean age 30 years; seven females, mean age 29 years) were tested on three occasions across the same day separated by a minimum of 2 h. An acoustic probe of 40-msec bursts of 116 dB(A) white noise over a continuous background noise of 70 dB(A) was presented binaurally through headphones and the eye-blink component of the startle response was measured taking electromyographic recordings from the right orbicularis oculi. The test session was identical at each time point and consisted of two blocks of 12 randomly mixed trials of four pulse-alone, four 60-msec prepulse and four 120-msec prepulse trials enclosed by two blocks each of six pulse-alone trials. There was huge variation in individual response magnitude that was independent of subsequent PPI in both women and men. Women showed greater PPI in the second half of sessions with the 120-msec prepulse only; but PPI was not altered significantly in either group between sessions across the day. In general, there was good test-retest reliability of PPI especially within trial type. Normal reflex habituation occurred across sessions and this effect was preserved in sessions across the day. Latency of response was significantly reduced in a session by the 60-msec trial type compared to the 120-msec trial type, as previously reported. Our results suggest that measures of PPI and habituation of the startle response are appropriate and reliable for a within-subject, test-retest design.
An examination of differences in the time course of oxazepam's effects on implicit vs explicit memory
Authors: Buffett-Jerrott Susan E. , Stewart Sherry H. , Bird Sally , Teehan Michael D.
Published: March 2007

The present study was designed to examine the effects of oxazepam on implicit vs explicit memory processes, as a function of this drug's time course. The effects of oxazepam (30 mg) or placebo on directly comparable tests of implicit memory (word stem completion) and explicit memory (cued recall) were examined at three time points: 100 min post-drug administration (prior to the theoretical peak plasma concentration of oxazepam; i.e. 'pre- peak' condition), 170 min post-drug (close to theoretical peak; i.e. 'peak' condition) or 240 min post-drug (following theoretical peak: i.e. 'post-peak' condition). Sixty healthy volunteers were randomly assigned to either the drug condition or the placebo condition in a double-blind design and were tested on both memory tests at one of the three time points. In the 'pre-peak' condition, oxazepam impaired cued recall performance relative to placebo but did not impair priming. In the 'peak' condition, oxazepam impaired performance on both memory tasks. In the 'post-peak' condition, cued recall performance in the oxazepam group remained significantly impaired relative to placebo. However, oxazepam-induced impairments in priming were only marginal, suggesting that oxazepam-induced impairments in implicit memory processes begin to wane following theoretical peak drug concentrations. The fact that oxazepam-induced priming impairments were significant only when the word stem completion task was administered close to peak plasma concentrations, supports the hypothesis that benzodiazepines exert time-dependent effects on implicit memory processes. The results also support the theoretical distinction between implicit and explicit memory processes, since the directly comparable implicit and explicit tasks showed different impairment curves over time.