bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of preference for nightly triazolam versus placebo in moderate social alcohol drinkers
Authors: Mintzer Miriam Z. , Allen Richard P. , Griffiths Roland R.
Published: April 2009

This study was designed to examine whether the widely prescribed benzodiazepine hypnotic triazolam has reinforcing effects in moderate social alcohol drinkers, without histories of drug abuse or insomnia, in the context of its use as a hypnotic. Eleven healthy adult volunteers who met criteria for ‘good sleepers’ participated in a 60-session double-blind choice study which was conducted on an outpatient basis with participants sleeping at home. Twenty three-session sampling/choice tests were conducted sequentially to provide 20 evaluations of the reinforcing effects of 0.25 mg/70 kg triazolam versus placebo, ingested orally 30 min before bedtime. Each three-session test consisted of two sampling sessions, in which participants received exposure to each of the two drug conditions in different colored capsules, followed by one choice session, in which participants were asked to choose one of the two colour-coded capsules for self-administration. Four participants exhibited a significant choice of triazolam, three, a significant choice of placebo (i.e. triazolam avoidance), and four, a random (i.e. non-significant) choice between triazolam and placebo. The reasons provided by participants were consistent with their choices and with the expected effects of triazolam versus placebo. Analyses of post-sleep questionnaires indicated that triazolam did not produce a clinically meaningful improvement in sleep. The finding that triazolam functioned as a reinforcer in participants without insomnia suggests that triazolam has reinforcing effects in some individuals for which hypnotic treatment is not clinically indicated, and that health care professionals must continue to assess the risk/benefit ratio of benzodiazepine hypnotic prescription.
Effects of d-amphetamine on the performance of rats in an animal analogue of the A-X Continuous Performance Test
Authors: Maes J. H. R. , Bouwman B. M. , Vossen J. M. H.
Published: April 2009

Schizophrenia patients subjected to the A-X Continuous Performance Test (A-X CPT) show cognitive deficits that are thought to reflect impaired representation and maintenance of context information. An issue deserving attention is to what extent the acute amphetamine model of schizophrenia also models these cognitive deficits. The present experiment examined the effect of acute d-amphetamine (AMP) on the performance of rats in an animal analogue of the A-X CPT. Subjects first learned to solve an A [.arrowright] X+, B [.arrowright] X–, A [.arrowright] Y– discrimination task, with A and B representing visual features; X and Y designating auditory target stimuli; [.arrowright] signifying a serial presentation; and + and – referring to food reinforcement and non reinforcement, respectively. Frequency of food-magazine visits was the dependent measure. After mastering the discrimination, rats received test trials under either saline or 0.5 mg/kg AMP (s.c.). At test, the interval between feature and target presentation was varied; reinforcement contingencies were maintained. AMP significantly impaired performance on the A [.arrowright] X+/B [.arrowright] X– discrimination by increasing the response level on B [.arrowright] X– trials. AMP did not significantly affect performance on the A [.arrowright] X+/A [.arrowright] Y– discrimination. However, AMP also increased magazine responding in the absence of the presentation of features and targets. A parsimonious conclusion based on these preliminary results is that acute AMP does not affect processing of context information provided by the visual features in this procedure. It rather has a more nonspecific response-enhancing effect, especially with respect to stimuli associated with the delivery of food.
Discriminative stimulus properties of indorenate, a 5-HT1A, 5-HT1B and 5-HT2C agonist: a study in rats
Authors: Sánchez H. , Velázquez-Martínez D. N.
Published: April 2009

Indorenate (INDO), initially described as an antihypertensive agent, also has some effects on behaviour, with anxiolytic and anorectic actions being reported. The aim of the present experiment was to examine the activity of INDO at the behavioural level at various serotonin (5-hydroxytryptamine, 5-HT) receptor sites by comparing its stimulus properties with those of other 5-HT receptor agonists and by examining its interactions with some 5-HT antagonists. Rats were trained to discriminate between 10.0 mg/kg INDO (administered intraperitoneally (90 min before the start of the session) from saline. A Fixed Ratio 10 (FR10) schedule of reinforcement was in effect in each drug condition. During generalization test sessions, the discrimination index (DI, responses to drug lever/responses to drug + saline lever) was calculated from the responses emitted before the first reinforcer of the session. DI was a function of the dose of INDO employed. Generalization to the discriminative stimulus properties of INDO was observed with the 5-HT1Areceptor agonist 8-OH-DPAT (1.0 mg/kg produced 90% generalization) and the 5-HT1B/2Creceptor agonist 1-(3-trifluoromethylphenyl) piperazine (TFMPP) (3.0 mg/kg produced up to 75% generalization). Yohimbine (5.6 mg/kg), buspirone (1.0 mg/kg), 6-chloro-2-(1-piperaziny)pyrazine (1.0 mg/kg) and m-chlorophenyl piperazine (mCPP) (1.0 mg/kg) induced a DI of 70%, 50% and 48% and 55%, respectively. In generalization tests, ritanserin (0.01–1.0 mg/kg) induced saline-like responding. NAN-190 (3.0 mg/kg), a 5-HT1Areceptor antagonist, was able to reduce the DI of INDO to 50%. Although the 5-HT2C/2Areceptor antagonists cinanserin (10.0 mg/kg) and metergoline (0.3 mg/kg) were able to reduce the stimulus properties of INDO to 60% and 30%, respectively, only ritanserin (1.0 mg/kg) reduced the stimulus properties of INDO to 25% with a clear dose–response relationship. The results suggest that INDO acts as an agonist at 5-HT1Areceptor sites, but its activity at 5-HT1B/2Creceptor sites also contributes to its discriminative function.
Neuroleptic malignant-like syndrome after abrupt withdrawal of baclofen
Authors: Turner M. R. , Gainsborough N.
Published: April 2009

We present the case of a 36-year-old man who presented with a clinically neuroleptic malignant-like syndrome involving disorientation, signs of autonomic dysfunction, rigidity and raised total creatine kinase level, but in the absence of any neuroleptic medication. He had, however, abruptly stopped taking his longterm baclofen in the days prior to presentation. He improved markedly after the reintroduction of baclofen, and we postulate that his clinical syndrome resulted from the sudden withdrawal of this drug. We concur with the concept that neuroleptic malignant syndrome represents a spectrum of disorders, and add it to the list of possible sequelae after abrupt withdrawal of baclofen.
Effect of repeated methylphenidate administration on presynaptic dopamine and behaviour in young adult rats
Authors: Sproson Eleanor J. , Chantrey Jonquille , Hollis Christopher , Marsden Charles A. , Fone Kevin C. F.
Published: April 2009

Methylphenidate, a dopamine reuptake inhibitor, is the most common treatment for attention-deficit hyperactivity disorder and may be prescribed for years, despite little evidence of any long-term benefit, nor knowledge of potential chronic side-effects. Therefore, this study examined the acute and longer-term behavioural effects and assessed striatal dopamine function following subchronic methylphenidate administration to adolescent rats. Male hooded Lister rats received methylphenidate (4 mg/kg i.p. twice daily for 4 days) or saline (1 ml/kg) and the acute locomotor and stereotype behaviour was monitored on days 1 and 4, novel object exploration on day 2 and, following 12 days drug withdrawal, the long-term effect examined on social interaction on day 16. Ex-vivo K+ (20 mM)- and methylphenidate (0.1 mM)-induced [3H]dopamine release from striatal slices and striatal monoamine content were measured on day 18. Compared with saline, methylphenidate induced mild hyperactivity without stereotypy but did not alter novel object exploration and, following withdrawal, had no long-term effect on social interaction. In striatal slices from controls, both K+ and methylphenidate elevated [3H]dopamine release (p < 0.01) while only combined treatment elevated release in methylphenidate pretreated rats, although striatal monoamine content was unaltered compared with control rats. In summary, a repeated dose of methylphenidate that had acute behavioural effects produced no long-term alteration in social interaction but attenuated presynaptic striatal dopamine function.
Validity and sensitivity of a pen computer battery of performance tests
Authors: Cameron E. , Sinclair W. , Tiplady B.
Published: April 2009

This study compared administration of performance tests and visual analogue scales (VAS) using a newly developed pen computer (PenC) battery with established tests using either pencil-and-paper (PP) or conventional computer. The performance of 47 subjects (23 male, age 18–45 years, weight 51–112 kg) was compared on the two systems after a dose of ethanol (0.8 g/kg up to a maximum of 60 g for males, 50 g for females) or placebo in a double-blind two-period randomized crossover study. Mean (SD) blood ethanol concentrations (breathalyser) were 94.5 mg/100 ml (21.9) at the start of the test battery (30 min post-drink) and 80.2 (13.0) at the end of the battery (75 min post-drink). Ethanol effects were found in all tests, with most outcome measures showing significant slowing or loss of accuracy. Results from the Rapid Visual Information Processing, Sentence Verification and Continuous Attention tasks show that the ethanol–placebo difference and the statistical significance of this difference are in close correspondence for the two modes of administration. The pen computer versions of these tasks may therefore be used as direct replacements for the previous versions. Digit–Symbol and maze tasks did not correspond so closely both showing differences in the speed-accuracy trade-off between the two modes. These tests, however, are sensitive to the effects of ethanol, and may be useful in their own right. Principal component analysis suggested that VAS may be grouped into two factors: (1) ‘functional integrity’, including measures of alertness and perceived proficiency, and (2) ‘mood’, including happiness and sociability. Factor 1 showed substantial effects of ethanol, while factor 2 was unchanged. There was close agreement between the results from PP and PenC for both factors as well as for the Sober-Drunk scale, which showed the expected effects of ethanol. Thus pen computer VAS perform in a similar way to the PP versions.
Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms
Authors: MacInnes N. , Handley S. L. , Harding G. F. A.
Published: April 2009

Previous work has indicated recreational use of methylenedioxymethamphetamine (MDMA or ecstasy) is associated with elevated scores on self-report measures of depression. We sought to examine the long-term effects of consumption on depression in a group of individuals who had consumed large quantities of the drug in the past, but were now leading relatively drug free lives. Respondents to this study (n = 29) had consumed an average of 1.5 ecstasy tablets in the last month, 8.4 in the last 6 months and 23.3 in the last 12 months. The estimated total consumed was 527 tablets, indicating that these respondents were indeed former chronic users of the drug. None of the respondents had consumed ecstasy in the last 14 days. Levels of depression (Beck's Depression Inventory) were significantly (p < 0.01) elevated compared to a matched non-drug using control group. Within the group of former chronic users, these levels of depression were not significantly affected by current use of alcohol, cannabis or amphetamine, but were positively correlated with an external locus of control (p< 0.05), infrequent but severe- (p< 0.05) and frequent but mild- (p< 0.005) self-report measures of life stress. Multiple regression indicated that levels of frequent but mild life stress (p< 0.005) and the quantity of ecstasy tablets respondents consumed over a 12-h period (p< 0.05) were the only variables that were significant predictors of self-reported levels of depression. The results of this study indicate that former chronic ecstasy users report higher levels of depression than their matched controls.
The lowest effective dose of fluoxetine in the forced swim test significantly affects the firing rate of lateral septal nucleus neurones in the rat
Authors: Contreras Carlos M. , Rodríguez-Landa Juan Francisco , Gutiérrez-García Ana G. , Bernal-Morales Blandina
Published: April 2009

The administration of a relatively high dose of antidepressant drugs produces an increased neuronal firing rate of the lateral septal nucleus (LSN) in the rat and a decreased immobility in rats forced to swim. However, it is unknown whether a minimally effective low-dose 21-day treatment with the selective serotonin reuptake inhibitor, fluoxetine, while reducing immobility in the forced swim test, also increases the neuronal firing rate of the LSN in Wistar rats. The total time of immobility decreased with a daily injection of 0.5, 1.0 or 2.0 mg/kg of fluoxetine (p< 0.001), and the lowest dose increasing the latency to the first immobility period (p < 0.0001) was 1.0 mg/kg. Therefore, the action of the 21-day fluoxetine treatment (1.0 mg/kg) on the firing rate of LSN neurones was tested in another group of rats. A total amount of 78 single-unit extracellular recordings was taken from the LSN of eight control rats (n = 40) and eight fluoxetine treated rats (n = 38). The LSN firing rate in the fluoxetine group was double (18.3 ± 2.5 spikes per 10 s, p< 0.05) that in the control group (7.0 ± 0.9 spikes per 10 s), and the first order interval of firing proved to be significantly lower in the fluoxetine group compared to the control group (384.3 ± 22.3 and 639.7 ± 27.5 ms, respectively; p < 0.05). In conclusion, the increased neuronal firing rate of the LSN in the animals treated with a low dose of fluoxetine may be associated with an increased motivation to escape from the stressful situation that the forced swim represents.
Comparison between noradrenergic and serotonergic medications using the Social Adjustment Scale: is drive enhancement necessary for recovery of social functioning?
Authors: Luty Suzanne E. , Joyce Peter R. , Mulder Roger T.
Published: April 2009

The Social Adjustment Scale (SAS) was used to assess social functioning sequentially over 13 weeks in a group of 188 depressed outpatients randomized to either the noradrenergic antidepressant, nortriptyline, or the selective serotonin reuptake inhibitor, fluoxetine. Over the period of 13 weeks, there were no differences in total SAS scores between the nortriptyline and the fluoxetine group. In comparing the SAS subscale scores, which may measure different areas of motivation and behaviour (drive), there were differences between the two groups in only two subscales. At 13 weeks, the group randomized to fluoxetine were more impaired in marital role (p = 0.026) whereas, at 6 weeks, the group randomized to nortriptyline were more impaired in friction scores (p = 0.012). These results do not support the concept of specific augmentation of drive-related behaviour by noradrenergic medication. This challenges the earlier findings relating to drive enhancement and social adjustment using such medication.
Effect of kava extract on vagal cardiac control in generalized anxiety disorder: preliminary findings
Authors: Watkins Lana L. , Connor Kathryn M. , Davidson Jonathan R. T.
Published: April 2009

Anxiety disorders are associated with low vagal control of heart rate and increased risk of cardiac mortality and sudden cardiac death. This study examined whether the herbal anxiolytic, kava, produces improvement in vagal control in generalized anxiety disorder. Before and after treatment with placebo (n = 7) or kava (n = 6), two indices of vagal control were measured under supine conditions using power spectral analysis: baroreflex control of heart rate (BRC) and respiratory sinus arrhythmia (RSA). Significantly more patients treated with kava showed improved BRC compared to the placebo group (p < 0.05). Furthermore, the magnitude of improvement in BRC was significantly correlated with the degree of clinical improvement (p < 0.05). RSA did not respond to treatment. These preliminary findings suggest that kava might exert a favourable effect on reflex vagal control of heart rate in generalized anxiety disorder patients. The parallel clinical and BRC responses may reflect an underlying common effect of this herbal anxiolytic.
Effects of ketanserin and haloperidol on prepulse inhibition of the acoustic startle (eyeblink) response and the N1/P2 auditory evoked response in man
Authors: Graham S. J. , Langley R. W. , Verduzco A. M. Balboa , Bradshaw C. M. , Szabadi E.
Published: April 2009

Contraction of the orbicularis oculi muscle in response to a sudden loud sound (acoustic startle response) and the N1/P2 component of the auditory evoked potential are both attenuated when a brief low-intensity stimulus is presented 30–500 ms before the ‘startle-eliciting’ stimulus (prepulse inhibition). Here, we report the effects of the serotonin (5-HT)2 receptor antagonist ketanserin and the D2 dopamine receptor blocking antipsychotic drug haloperidol on these responses. Fifteen males (aged 18–35 years) participated in four sessions at 7-day intervals, in which they received ketanserin 20 mg, ketanserin 40 mg, haloperidol 3 mg and placebo, according to a balanced double-blind design. Electromyographic (EMG) responses of the orbicularis oculi muscle and N1/P2 auditory evoked potentials were recorded in a 20-min session, 3 h after ingestion of haloperidol or 1 h after ingestion of ketanserin. Subjects received 40 trials in which 1-kHz sounds were presented: (i) 40 ms, 115 dB (‘pulse alone’ trials), and (ii) 40 ms, 85 dB, followed after 120 ms by 40 ms, 115 dB (‘prepulse/pulse’ trials). Mean amplitudes of the EMG response and the N1/P2 potential were derived from the pulse-alone trials and, in each case, percentage prepulse inhibition was calculated. Serum prolactin was measured after each treatment, and autonomic (heart rate, blood pressure, salivation) and psychological (visual analogue self-ratings of mood and alertness, critical flicker fusion frequency) measures were taken before and after each treatment. Ketanserin 40 mg significantly reduced the amplitude of the EMG response and both doses of ketanserin significantly suppressed prepulse inhibition of the response; haloperidol had no effect on EMG response amplitude or prepulse inhibition. Neither drug affected N1/P2 amplitude or prepulse inhibition of this response. Ketanserin, but not haloperidol, reduced subjective alertness and critical flicker fusion frequency. Haloperidol, but not ketanserin, elevated serum prolactin level. These results confirm that prepulse inhibition of the startle response and of the N1/P2 complex have different pharmacological sensitivities. The ability of ketanserin to attenuate the startle response may reflect its sedative action, as other drugs with sedative properties have also been found to attenuate the startle response in man. The ability of ketanserin to suppress prepulse inhibition of the startle response is consistent with previous evidence for the involvement of 5-HTergic mechanisms in the regulation of prepulse inhibition in man.
A possible association between high normal and high dose olanzapine and prolongation of the PR interval
Authors: Kosky Nick
Published: April 2009

Two cases of light-headedness or ‘fainting’ in patients with schizophrenia treated with olanzapine are presented. Electrocardiogram investigation revealed first-degree heart block on high normal and high dose olanzapine, which normalized after dose reduction.
Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man
Authors: Schmitt Jeroen A. J. , Ramaekers Johannes G. , Kruizinga Monique J. , van Boxtel Martin P. J. , Vuurman Eric F. P. M. , Riedel Wim J.
Published: April 2009

There is evidence for a specific impairment of human vigilance following enhancement of serotonergic activity by antidepressant drugs. In the present study, we investigated the putative role of serotonergic–dopaminergic interactions in diminished vigilance by comparing the attentional effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) with additional mild dopamine stimulating effects, with those of paroxetine, a SSRI without dopamine activity, using a placebo-controlled, double-blind, three-way cross-over design. Twenty-one (of 24) healthy middle-aged subjects completed the three treatment periods of 2 weeks in which sertraline (50 mg, days 1–7; 100 mg, days 8–14), paroxetine (20 mg, days 1–7; 40 mg, days 8–14) and placebo were administered. Vigilance (Mackworth Clock Test), selective (Stroop, Dichotic Listening) and divided attention (Dichotic Listening) were assessed at baseline and on days 7 and 14 of each treatment period. Selective and divided attention were unaffected by SSRI treatment. Subchronic administration of paroxetine impaired vigilance performance at each investigated dose. Sertraline did not produce a significant decline in vigilance performance, presumably due to its concomitant effects on dopamine activity, counteracting the negative effects of serotonin on dopamine neurotransmission. It is concluded that a serotonergically mediated reduction of dopamine activity plays an important role in the reduction of human vigilance following SSRI administration.
Characterization of olanzapine-induced weight gain in rats
Authors: Goudie Andrew J. , Smith Judith A. , Halford Jason C. G.
Published: April 2009

Novel antipsychotic drugs (APDs) have enhanced therapeutic actions compared to ‘typical’ APDs. However,clinical studies indicate that some induce marked weight gain. We attempted to model this effect in female Wistar rats given olanzapine chronically at 4 mg/kg b.i.d (4.5 h between injections). Such rats showed marked weight gain, which was statistically significant after only a single day of treatment, although weight gain increased up to a plateau after 10 days of treatment. Cessation of treatment led to rapid weight loss, which was significant after a single day of withdrawal. The weight gain observed was characterized by marked individual differences. As some clinical reports suggest that novel APD-induced weight gain is most pronounced in patients with the lowest body weight, we examined the relationship between weight gain and baseline body weight. However, we observed no significant relationship between baseline body weight and weight gain. The observation that olanzapine can induce weight gain rapidly in rats, in conjunction with the observation of marked individual differences in weight gain, suggests that patients at risk of developing weight gain might be detectable early in treatment. Furthermore, the finding that weight gain is rapidly reversible suggests that patients at risk of weight gain could be switched to APDs with less pronounced tendencies to induce weight gain. The study of APD-induced weight gain in rodents may provide insights into the nature, causes, and treatments for, novel APD-induced weight gain in the clinic. However, it remains to be determined how closely rodent models mimic the clinical situation and whether the mechanism(s) involved in the weight gain we have observed are the same as those involved in the clinical use of these drugs.
Opposite effects of ethanol and ketamine in the elevated plus-maze test in Wistar rats undergoing a chronic oral voluntary consumption procedure
Authors: Silvestre Jordi S. , Pallarés Marc , Nadal Roser , Ferré Núria
Published: April 2009

The anxiolytic effects of ethanol (EtOH) have been involved in the vulnerability to EtOH drinking in humans. However, the role of the anxiolytic effects of EtOH during a chronic ingestion of the drug has not been extensively addressed, either in humans or in animal models. Since it was first shown that EtOH interacts with the N-methyl-d-aspartate (NMDA) receptor, a growing body of evidence demonstrating the involvement of this receptor in a wide range of EtOH effects has been reported. The present study aimed to investigate the ability of a voluntary consumption of EtOH to exert its putative anxiolytic-like activity in non-selected male Wistar rats held under a voluntary chronic oral consumption procedure using the elevated plus-maze (EPM) test. The effects of EtOH were compared with those of the noncompetitive NMDA receptor antagonist ketamine (KET), and with a mixture of both drugs. Rats were provided with 1-h limited access to one of the following sweetened (10% w/v glucose) solutions: (i) control; (ii) EtOH (ethanol, 10% v/v); (iii) KET (ketamine HCl, 0.28 mg/ml); or (iv) mixed (EtOH 10% v/v plus ketamine HCl 0.28 mg/ml) for 35 consecutive days. At the end of this period, and immediately after the last 1-h access to the respective solution, animals were independently tested in either EPM or open field tests. Previously, rats were tested on the inclined screen test during 15 consecutive days. The opposite effects were observed with EtOH and KET consumption in the EPM test, with EtOH decreasing and KET increasing the percentage of time spent in the open arms of the EPM, which was shown to be independent of any locomotor impairment, whereas consumption of the mixed solution did not significantly affect any test. Since the EtOH did not exhibit anxiolytic-like effects after its chronic oral consumption, it might be hypothesized that the anxiolytic activity of the EtOH is not critically involved in the maintenance of a voluntary EtOH consumption in non selected rats. On the other hand, the lack of effects from mixed solution consumption suggests that EtOH and KET may interact in such a way that their effects are neutralized.
Evaluation of tests of central nervous system performance after hypoxemia for a model for cognitive impairment
Authors: Van der Post J. , Noordzij L. A. W. , de Kam M. L. , Blauw G. J. , Cohen A. F. , van Gerven J. M. A.
Published: April 2009

The sensitivity of several neurophysiological and cognitive tests to different levels of hypoxia was investigated. Cerebral hypoxia in healthy volunteers may be a disease model for dementia or other forms of brain dysfunction. Twelve healthy subjects were included in a randomized, single-blind, placebo-controlled, three-period cross-over trial. They received three air/N2 gas mixtures via mask breathing [aimed at peripheral oxygen saturation (SPO2) values of > 97% (placebo), 90% and 80%, with normal end-tidal CO2]. Central nervous system effects were tested regularly for 130 min by saccadic and smooth pursuit eye movements, electro-encephalogram, visual analogue scales and cognitive tests. Treatments were well tolerated. Compared to SPO2 90%, SPO2 80% reduced saccadic peak velocity by 16.4 °/s [confidence interval (CI) –26.3, –6.4], increased occipital delta power by 14.3% (CI 3.6, 25.1), and significantly increased most cognitive reaction times. SPO2 80% also decreased correct responses for the binary choice task and serial word recognition [–1.3 (–2.2, –0.3) and –3.5 (–6.2, –0.8), respectively] compared to SPO2 90%. Cognitive performance was decreased by SPO2 80% and increased by SPO2 90% compared to placebo. Sensitive effect measurements can be identified for these interventions. The applicability as a model for cognitive impairment should be investigated further.
The prescription of dexamphetamine to patients with schizophrenia and amphetamine dependence
Authors: Carnwath Tom , Garvey Tim , Holland Mark
Published: April 2009

Patients with a severe mental illness such as schizophrenia have significant rates of concurrent amphetamine use. Such dual diagnosis patients have been shown to have poorer treatment outcomes. Often, they do not comply with treatment plans and have frequent episodes of hospitalization. There is growing evidence for the role of prescribed dexamphetamine in the treatment of amphetamine dependence. The prescription of dexamphetamine to patients with schizophrenia and amphetamine dependence has not been previously reported. Eight schizophrenic patients are described to whom dexamphetamine has been prescribed, with information being extracted retrospectively from case notes. In four out of eight cases, the prescription of dexamphetamine led to apparently good progress both in terms of substance misuse and psychiatric health. In two cases, progress was more equivocal, but appeared to produce some benefit. Two cases could be judged as treatment failures, but the condition and situation of the patients were not worse at the end of treatment than at the beginning. Compliance with neuroleptics increased in most cases. No patients exhibited exacerbation of psychosis as a result of treatment. The rate of outcome success is satisfactory when consideration is given to the difficult nature of this patient group, and their previous failure to respond to intensive treatment. It is argued that benefits may be gained from increased compliance with psychiatric treatment in patients prescribed amphetamine, and that this may outweigh possible risks. However, any conclusions are tentative in view of the nature of this study. A small open-label prospective study is recommended.
Maintained improvement with minocycline of a patient with advanced Huntington's disease
Authors: Denovan-Wright E. M. , Devarajan S. , Dursun S. M. , Robertson H. A.
Published: April 2009

We present the case of a patient with advanced Huntington's disease treated with minocycline. Minocycline (but not tetracycline which does not cross the blood–brain barrier) appears to increase longevity in an animal model for Huntington's disease. The patient has been maintained on minocycline for more than 1 year with positive effects. Cessation of minocyclin for 3 weeks resulted in an exacerbation of symptoms. The animal studies have suggested that minocycline may prevent progression of Huntington's disease and other neurological disorders. By contrast, this present result suggests that minocycline may benefit those with advanced Huntington's disease and can be used safely in these patients.
Memory for emotional material: a comparison of central versus peripheral beta blockade
Authors: O'Carroll R. E. , Drysdale E. , Cahill L. , Shajahan P. , Ebmeier K. P.
Published: April 2009

The connection between affect and memory is poorly understood. A possible psychopharmacological linking mechanism is the sympathetic arousal that occurs in response to threatening or emotive material. Cahill et al. (1994) reported that a single administration of 40 mg propranolol hydrochloride, a non-selective b-adrenergic blocker, to healthy young adults significantly reduced delayed recall of emotive material, with recall of matched neutral material unaffected. This study differed importantly from the original Cahill et al. (1994) procedure in that only the emotionally arousing narrative was employed. Using the same slide presentation as Cahill et al. (1994), an experiment was carried out in order to determine whether b-adrenergic blockade significantly reduces recall of emotive material via a central or peripheral mode of action. Thirty-six healthy young adults were recruited as subjects. Subjects were randomly allocated to three groups: (a) placebo (b) 40 mg propranolol hydrochloride (a beta blocker which readily crosses the blood–brain barrier) and (c) 40 mg nadolol (a beta blocker which does not cross the blood–brain barrier). The three groups were matched for age, sex, intelligence, personality factors, and general memory functioning. Subjects viewed a series of 11 slides accompanied by a narrative, divisible into three phases. The emotionally arousing component of the narrative was introduced during phase II. Both central and peripheral beta blockade produced the expected effects on the sympathetic nervous system, as demonstrated by reliable reductions in systolic and diastolic blood pressure. In a surprise memory test 1week later, subjects were asked to recall as much as possible of the story and slides, and also completed a forced choice recognition memory test. All three groups showed heightened recall and recognition for the central (emotive) section of the story. There was no differential effect of beta blockade (either central or peripheral) relative to placebo. Beta blockade markedly reduced systolic and diastolic blood pressure, but resulted in no significant effect on memory for both emotional and neutral material.
A re-evaluation of social defeat as an animal model of depression
Authors: Marrow Lynne P. , Overton Paul G. , Brain Paul F
Published: April 2009

Social defeat by aggressive Tryon Maze Dull (TMD) rats, resulting in loss of rank of a previously dominant rat, has recently been advanced as a model of loss of self-esteem in humans. Since low self-esteem is a major symptom of depression, a further claim has been made that loss of rank can be used as a model of depression. In support of this claim, it has been suggested that loss of rank can be reversed by the antidepressant imipramine. However, antidepressant treatment has not yet been shown to reverse the effects of defeat for more than a single test session. Consequently, the present study was designed to more fully assess the effects of antidepressant treatment on the behaviour of defeated animals. Six pairs of male Lister Hooded (LH) rats were observed biweekly for 30 min at the onset of the dark phase of the light-dark cycle. In five of the six pairs, a stable social hierarchy (assessed by the observation of aggressive behaviours such as attacks and pushes, and submissive behaviours such as submissive posture) was established over a period of 10 weeks. The dominant animals of these five pairs were defeated once a week, in the home cage, by a singly housed male TMD for a period of 15 min. After 5 weeks of defeat by TMD, all five of the dominant animals showed an effect of defeat on behaviours relevant to status, although a reversal in status within the LH pairs was apparent in only one case. All defeated animals, regardless of whether or not defeat affected status, received daily injections of imipramine (5 mg/kg) for 5 weeks. Imipramine markedly worsened behaviours relevant to status in the treated animals. Indeed, animals treated with imipramine were more likely to lose encounters with their cage-mates. Consequently, the results cast doubt on the validity of social defeat as a model of depression, at least when the effects of defeat are assessed in terms of social status.
Quinolinic acid inhibits DOI-induced head shakes in mice
Authors: Kariyawasam S. Himani , Handley Sheila L.
Published: April 2009

Quinolinic acid, a metabolite of tryptophan in the kynurenine pathway, inhibited the 5-HT2A/2C direct agonist (+)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino propane hydrochloride (DOI) induced head shakes in mice in a dose-dependent manner. This e¡ect was observed 10 min after intracerebroventricular (i.c.v.) administration of 0.06251 mg/mouse. 3-Hydroxyanthranilic acid, which is the immediate stable precursor of quinolinic acid in the kynurenine pathway, showed a similar e¡ect 60120 min after subcutaneous (s.c.) administration, without showing any e¡ect 10 min after i.c.v. administration or 2040 min after s.c. administration. These observations suggest that quinolinic acid can alter central e¡ects mediated via 5-HT2A receptors.
Magnetic resonance imaging and magnetic resonance spectroscopy assessment of brain function in experimental animals and man
Authors: Morris Peter G.
Published: April 2009

This paper introduces the basic principles and techniques of functional magnetic resonance imaging (fMRI) and spectroscopy (MRS). Examples are given of single event human fMRI studies on control subjects, and a graded activation protocol applied to Parkinsonian patients. Possibilities are discussed for using fMRI techniques to study the neural substrate of various pharmacological agents, including drugs of abuse.The application of these pharmacological MRI (phMRI) studies to animal models and the associated technical issues are also addressed. The use of MRS in studying brain status and function is reviewed, with particular emphasis on 13C isotopic labelling studies.
The effects of the novel anxiolytic drug lesopitron, a full and selective 5-HT1A receptor agonist, on pupil diameter and oral temperature in man: comparison with buspirone
Authors: Phillips M. A. , Szabadi E. , Bradshaw C. M.
Published: April 2009

We investigated the effects of two 5-HT1Areceptor agonists, buspirone and lesopitron, upon pupil size in human volunteers at an ambient luminance level of 32 Cd m72and in darkness. Pupil diameter was monitored with a binocular infrared television pupillometer, before and after the administration of treatments for 4 h at 20-min intervals. Two experiments were conducted. In Experiment 1, 14 healthy male volunteers participated in seven weekly sessions, each associated with the ingestion of one capsule (buspirone 5, 10 and 20 mg, lesopitron 10, 20 and 40 mg and placebo), according to a double-blind balanced, cross-over design. Both buspirone and lesopitron tended to decrease pupil diameter. In darkness, only the highest dose of buspirone (20 mg) caused a miosis that was statistically significant. However, at the luminance level of 32 Cd m72buspirone 10 and 20 mg evoked statistically significant miotic effects, as did the highest dose of lesopitron (40 mg). The miotic effect was significantly greater at 32 Cd m72than in darkness after each dose of buspirone and the highest dose (40 mg) of lesopitron. In Experiment 2, pupil diameter and oral temperature were monitored with an electronic thermometer at 40-min intervals. Twenty healthy male volunteers participated in two weekly sessions, each associated with the sublingual application of 100 ml hydroalcoholic solution (lesopitron 20 mg, placebo), according to a double-blind balanced cross-over design. Lesopitron caused a significant miosis both in darkness and at the luminance level of 32 Cd m72; the miosis was greater at 32 Cd m72than in darkness. Lesopitron tended to decrease oral temperature; this effect however, was not statisically significant. The greater effectiveness on the pupil of lesopitron administered sublingually in a solution indicates the importance of first-pass metabolism in reducing the effectiveness of the drug when administered by the mouth. The miosis observed in both experiments may be due to either a sympatholytic or a parasympathomimetic effect of the drugs, or both. The light-dependence of the miosis indicates that the 5-HT1Areceptor agonists can modulate the light reflex, possibly via the noradrenergic control of central cholinergic neurones in the Edinger-Westphal nucleus.
Your Money or Your Health: Time Preferences and Trading Money for Health
Authors: Chapman Gretchen B.
Published: April 2009

Background. Time preferences reflect how future outcomes are valued relative to present ones. Previous research has found that time preferences for one domain (say, money) are inconsistent (uncorrelated) with those from another (say, health). The present studies evaluated whether this domain independence was due to decision makers’ sensitivity to a normatively appropriate principle about the tradability of health and money. Method. Participants read a scenario in which health and money were described as tradable or not tradable and then responded to hypothetical intertemporal trade-off questions. Results. In experiment 1, participants showed higher agreement between health and money time preferences in the tradable condition, as predicted. In experiment 2, participants responded from either an individual decision maker or policy maker perspective. Perspective had little effect on agreement between health and money discount rates, but there was again higher agreement in the tradable as compared to the not-tradable condition. Conclusion. Previous demonstrations of domain independence may have been due in part to decision makers’ assumption that health and money are not tradable.
Randomized Trial of a Patient Decision Aid for Choice of Surgical Treatment for Breast Cancer
Authors: Goel Vivek , Sawka Carol A. , Thiel Elaine C. , Gort Elaine H. , O’Connor Annette M.
Published: April 2009

A decision aid for the surgical treatment of early breast cancer was evaluated in a randomized controlled trial. The decision aid, a tape and workbook, includes explicit presentation of probabilities, photographs and graphics, and a values clarification exercise. Community surgeons were randomized to use the decision aid or a control pamphlet. Patients completed a questionnaire prior to using the decision aid, after reviewing it but prior to surgery, and 6 months after enrollment. There was no difference in anxiety, knowledge, or decisional regret across the 2 groups. There was a nonsignificant trend toward lower decisional conflict in the decision aid group. A subgroup of women who were initially leaning toward mastectomy or were unsure had lower decisional conflict. Although the decision aid had minimal impact on the main study outcomes, a subgroup may have benefited. Such subgroups should be identified, and appropriate decision support interventions should be developed and evaluated.
A Comparison of Bayesian Methods for Profiling Hospital Performance
Authors: Austin Peter C.
Published: April 2009

There is a growing interest in the use of Bayesian methods for profiling institutional performance. In the literature, several studies have compared different frequentist methods for classifying hospitals as performance outliers. The purpose of this study was to compare 4 different Bayesian methods for classifying hospitals as outcomes outliers, using 30-day hospital-level mortality rates for a cohort of acute myocardial infarction patients as a test case. The 1st Bayesian method involved determining the probability that a hospital’s mortality rate for an average patient exceeded a specified threshold. The 2nd method involved ranking hospitals according to their mortality rate for an average patient. The 3rd method involved determining the probability that a hospital’s standardized mortality ratio exceeded a specified threshold. The 4th method involved ranking hospitals according to their standardized mortality ratio. In most of the scenarios examined, there was only marginal agreement between the different methods. In only 4 of 19 comparisons, was there good agreement between the different methods (0.40 kappa 0.75). Methods based on ranking institutions were relatively insensitive to differences between hospitals. These inconsistencies raise questions about the choice of methods for classifying hospital performance, and they suggest a need for urgent research into which methods are best able to discriminate between institutions and which are most meaningful to decision makers.
Reduction Mammaplasty: Defining Medical Necessity
Authors: Kerrigan Carolyn L. , Collins E. Dale , Kim H. Myra , Schnur Paul L. , Wilkins Edwin , Cunningham Bruce , Lowery Julie
Published: April 2009

The authors evaluated existing and new criteria for defining the medical necessity for breast reduction surgery. Two cohorts of women (those requesting breast reduction surgery [N = 266] and a group of controls [N = 184]) completed a questionnaire including breast-specific symptom severity, the Short Form 36, the EuroQol, the McGill Pain Questionnaire, and the Multidimensional Body Self Relations Questionnaire. To evaluate prediction validity, the most widely accepted decision criteria and a new definition of medical necessity were applied to the data set to determine whether women meeting the definition had more favorable outcomes than those who did not as measured by validated self-report instruments. For existing criteria, women not meeting and meeting the criterion gained equal benefit from surgery. Women meeting the new definition (2 of 7 physical symptoms all or most of the time) had significantly greater improvement scores on 4 of the 5 health burden measures compared to women not meeting this definition. The authors conclude that medical necessity for breast reduction surgery is better defined by self-report of symptoms than by existing criteria.
Cultural Transmission of Uxorilocal Marriage in Lueyang, China
Authors: Li Shuzhuo , Feldman Marcus W. , Li Nan
Published: April 2009

In this article, the authors report on a study of the cultural transmission of uxorilocal marriage in Lueyang, China. They find that uxorilocal marriage has been commonly accepted and practiced in Lueyang since the beginning of this century, and uxorilocal marriage has been both a contingent and an institutional option for farmers with both preservative and practical purposes. Causes underlying contingent uxorilocal marriage are mostly demographic, and causes underlying institutional uxorilocal marriage are mostly economic, but a weak patriarchal family system, lack of dominant family clans in villages, and relaxed village regulation of uxorilocal marriage in Lueyang also play decisive roles. The occurrence of uxorilocal marriage is transmitted both from parents to children and from nonparental members of communities to couples. Rural economic reform since 1978 has had important influences on the transmission effects of uxorilocal marriage.
Gender, Property, and Retirement Strategies in Early Modern Northwestern Spain
Authors: Poska Allyson M.
Published: April 2009

Demographic studies indicate that elderly women were a prominent part of early modern rural society. Particularly in northwestern Spain, where partible inheritance left women in control of significant property, older women played a critical role in determining not only their own elder care but intergenerational relationships and family economies as well. An examination of retirement contracts from the region of Galicia in northwestern Spain indicates that peasant women used their familial authority and wealth to ensure that they and their families would be properly cared for as they aged.
The Course of the Marriage of Elizabeth Montagu: An Ambitious and Talented Woman Without Means
Authors: Hill Bridget
Published: April 2009

Based on a study of the Montagu Collection of letters housed in the Huntington Library, this article analyzes the apparent motives behind the marriage between Elizabeth and Edward Montagu and the slow but sure emergence of evidence of her growing dissatisfaction with it. It reveals the various ways in which she sought distraction from her marriage and her attempts to compensate for it. Behind her growing restlessness and frustration, there lie aspects of her character—her obsession with money, her urgent need to be constantly admired and lauded, and her need to be in control of both people and things.
Registered Households and Micro-Social Structure in China: Residential Patterns in Three Settlements in Beijing Area
Authors: Zhao Zhongwei
Published: April 2009

A large amount of research on Chinese households has been undertaken since 1980. However, problems existing in Chinese household registration and their impact on collecting household data have not been fully appreciated. Furthermore, most published studies have concentrated on the composition of households, while kinship relations beyond households have not been adequately investigated. This article starts with a description of China’s household registration and its connection with the census and survey data collection. Then, problems of household registration and their influence on the study of Chinese households are investigated on the basis of field research. Finally, village kinship networks are examined in order to shed further light on micro-social structure in rural China.