bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal development of CA3 pyramidal neurons and their afferents in the Ammon's horn of rhesus monkeys
Authors: Seress László , Ribak Charles E.
Published: May 2005

Previous studies described the postnatal development of CA3 pyramidal neurons and their afferents in the rat. However, the postnatal development of the primate hippocampus was not previously studied. Thus, pyramidal neurons of the CA3 area of the monkey hippocampus were analyzed postnatally in the present study. At birth, a few thorny excrescences, the complex spines postsynaptic to mossy fibers, were found on the proximal segments of both apical and basal dendrites, whereas distal dendrites displayed pedunculate spines. Thorny excrescences increased in number until the third month. A continuous increase in the number of spines per unit length along the distal dendrites was observed during the first 12 months. The ultrastructural features of somata and dendrites of pyramidal cells in newborn monkeys were similar to those of adults.

The analysis of the afferents to the CA3 pyramidal neurons was limited to the development of mossy fibers, the axons of granule cells, and myelinated axons in the alveus, stratum oriens, and stratum lacunosum‐moleculare. At birth, most mossy fiber terminals were densely packed with synaptic vesicles and formed mainly axospinous synapses with CA3 pyramidal cells. By 1 month of age, the number of mitochondria and embedded spines increased to mature amounts. In the first postnatal month, degenerating axons and axon terminals were frequently observed in the mossy fiber bundles in stratum lucidum. The proportion of myelinated axons increased simultaneously in all three examined layers. At birth most axons were unmyelinated, whereas at 7 months of age the proportion of myelinated axons was similar to that found in adults.

The present study indicates that most pyramidal neurons of the CA3 region in monkeys are in an advanced stage of development at the time of birth. Thus, mossy fibers from granule cells in the dentate gyrus have established mature‐looking synapses, and the thorny excrescences of pyramidal cells that are postsynaptic to mossy fibers are also adult‐like. Nevertheless, several of the adult features, such as the spine density of distal dendrites of pyramidal neurons and the myelination of afferent axons, develop during an extended period of time in the first year. The significance of this early anatomical maturation in a brain region involved in memory function is consistent with recent behavioral data that show a rapid postnatal maturation of limbic‐dependent recognition memory in rhesus monkeys. © 1995 Wiley‐Liss, Inc.
Connection matrix of the hippocampal formation: I. The dentate gyrus
Authors: Patton Paul E. , McNaughton Bruce
Published: May 2005

The hippocampal formation presents a special opportunity for realistic neural modeling since its structure, connectivity, and physiology are better understood than that of other cortical components. A review of the quantitative neuroanatomy of the rodent dentate gyrus (DG) is presented in the context of the development of a computational model of its connectivity. The DG is a three‐layered folded sheet of neural tissue. This sheet is represented as a rectangle, having a surface area of 37 mm2 and a septotemporal length of 12 mm. Points, representing cell somata, are distributed in the model rectangle in a roughly uniform fashion. Synaptic connectivity is generated by assigning each presynaptic cell a spatial zone representing its axonal arbor. For each postsynaptic cell, a list of potential presynaptic cells is compiled, based on which arbor zones the given postsynaptic cell falls within. An appropriate number of presynaptic inputs are then selected at random. The principal cells of the DG, the granule cells, are represented in the model, as are non‐principal cells, including basket cells, chandelier cells, mossy cells, and GABAergic peptidergic polymorphic (GPP) cells. The neurons of layer II of the entorhinal cortex are included also. The DG receives its main extrinsic input from these cells via the perforant path. The basket cells, chandelier cells, and GPP cells receive perforant path and granule cell input and exert both feedforward and feedback inhibition onto the granule cells. Mossy cells receive converging input from granule cells and send their output back primarily to distant septotemporal levels, where they contact both granule cells and non‐principal cells. To permit numerical simulations, the model must be scaled down while preserving its anatomical structure. A variety of methods for doing this exist. Hippocampal allometry provides valuable clues in this regard. © 1995 Wiley‐Liss, Inc.
Dehydroepiandrosterone sulfate suppresses hippocampal recurrent inhibition and synchronizes neuronal activity to theta rhythm
Authors: Steffensen Scott C.
Published: May 2005

Several neurosteroids have proconvulsant and memory‐en‐hancing properties and are potent modulators of the γ‐amino butyric acid (GABA) receptor/chloride‐ionophore complex. The effects of in situ microelectrophoretic application of the natural sulfate ester of the neurosteroid dehydroepiandrosterone (DHEAS) on evoked field responses and single‐unit activity were evaluated in the dentate gyrus and CA1 hippocampal subfield of halothane‐anesthetized rats. The effects of endogenous stimulation of DHEAS by in situ micropressure application of Trilostane ((4α, 5α, 17β)‐4, 5‐epoxy‐3, 17‐dihydroxyandrost‐2‐ene‐2‐carbonitrile (WIN24540)), an inhibitor of 3β‐hydroxysteroid dehydrogenase/isomerase (3β‐HSD), the enzyme that metabolizes DHEAS, on evoked responses and cellular activity in the hippocampus were also investigated. In situ microelectrophoretic application of DHEAS or micropressure application of Trilostane into CA1 markedly increased population excitatory postsynaptic potential (pEPSP) slopes and population spike (PS) amplitudes. Neither DHEAS nor Trilostane altered dentate pEPSP slopes or PS amplitudes, but both increased the amplitude of a late component of the pEPSP. Both DHEAS and Trilostane abolished GABA‐mediated pairedpulse inhibition in both the dentate and CA1. In addition, both DHEAS and Trilostane markedly increased the spontaneous firing rate of dentate hilar interneurons (INTs: 256% and 185%), CA1 pyramidal cells (PCs: 95% and 105%), and CA1 oriens/alveus (O/A) interneurons (179% and 85%) and synchronized their firing to hippocampal theta rhythm induced by tail‐pinch. These findings indicate that exogenous application and endogenous stimulation of DHEAS modulates hippocampal GABA inhibition in a physiologically relevant manner possibly by entraining hippocampal neurons to theta rhythm. © 1995 Wiley‐Liss, Inc.
Stable maintenance of glutamate receptors and other synaptic components in long‐term hippocampal slices
Authors: Bahr Ben A. , Kessler Markus , Rivera Santiago , Vanderklish Peter W. , Hall Randy A. , Mutneja Manpreet Singh , Gall Christine , Hoffman Keith B.
Published: May 2005

Cultured hippocampal slices retain many in vivo features with regard to circuitry, synaptic plasticity, and pathological responsiveness, while remaining accessible to a variety of experimental manipulations. The present study used ligand binding, immunostaining, and in situ hybridization assays to determine the stability of AMPA‐ and NMDA‐type glutamate receptors and other synaptic proteins in slice cultures obtained from 11 day postnatal rats and maintained in culture for at least 4 weeks. Binding of the glutamate receptor ligands [3H]AMPA and [3H]MK‐801 exhibited a small and transient decrease immediately after slice preparation, but the binding levels recovered by culture day (CD) 5–10 and remained stable for at least 30 days in culture. Autoradiographic analyses with both ligands revealed labeling of dendritic fields similar to adult tissue. In addition, slices at CD 10–20 expressed a low to high affinity [3H]AMPA binding ratio that was comparable with that in the adult hippocampus (10:1). AMPA receptor subunits GluR1 and GluR2/3 and an NMDA receptor subunit (NMDAR1) exhibited similar postcutting decreases as that exhibited by the ligand binding levels, followed by stable recovery. The GluR4 AMPA receptor subunit was not evident during the first 10 CDs but slowly reached detectable levels thereafter in some slices. Immunocytochemistry and in situ hybridization techniques revealed adult‐like labeling of subunit proteins in dendritic processes and their mRNAs in neuronal cell body layers. Long‐term maintenance was evident for other synapse‐related proteins, including synaptophysin, neural cell adhesion molecule isoforms (NCAMs), and an AMPA receptor related antigen (GR53), as well as for certain structural and cytoskeletal components (e. g., myelin basic protein, spectrin, microtubule‐associated proteins). In summary, following an initial and brief depression, many synaptic components were expressed at steady‐state levels in long‐term hippocampal slices, thus allowing the use of such a culture system for investigations into mechanisms of brain synapses. © 1995 Wiley‐Liss, Inc.
Postischemic inhibition of GABA reuptake by tiagabine slows neuronal death in the gerbil hippocampus
Authors: Inglefield Jon R. , Perry Jean M. , Schwartz Rochelle D.
Published: May 2005

The neuroprotective effects of enhancing neuronal inhibition with a γ‐aminobutyric acid (GABA) uptake inhibitor were studied in gerbil hippocampus following transient ischemia. We used in vivo microdialysis to determine a suitable dosing regimen for tiagabine (NNC 328) to elevate extracellular levels of GABA within the hippocampus. In anesthetized (normothermic) gerbils, tiagabine (45 mg/kg, i. p.) selectively elevated extracellular GABA levels 450% in area CA1 of the hippocampus. In gerbils subjected to cerebral ischemia via 5‐min bilateral carotid occlusion, extracellular GABA levels increased 13‐fold in area CA1, returning to baseline within 30–45 min. When tiagabine was injected 10 min following onset of reperfusion, GABA levels remained elevated (200–470%) for 90 min. In addition, tiagabine significantly reduced the ischemic‐induced elevation of glutamate levels in area CA1 during the postischemic period when GABA levels were elevated. There was no effect of postischemic tiagabine on aspartate or six other amino acids. Using the same dosing regimen, we evaluated the degree of neuroprotection in the hippocampus of gerbils 4 and 21 days after ischemia. Tiagabine decreased body temperature a maximum of 2.7°C beginning 30 min into reperfusion and lasting 90 min. In untreated gerbils sacrificed 4 and 21 days after ischemia, there was severe necrosis (99%) of the pyramidal cell layer in area CA1. Whereas tiagabine significantly protected the CA1 pyramidal cell layer in ischemic gerbils at 4 days (overt necrosis confined to about 17% of area CA1), the protection diminished significantly 21 days postischemia. When normothermia was maintained both during and after ischemia in a separate group of tiagabine‐treated animals, approximately 77% of the CA1 pyramidal cell layer was necrotic at 4 days. Based on these findings, we suggest that (1) tiagabine slows the development of hippocampal degeneration following ischemia, and (2) that mild, postischemic hypothermia is responsible, in large part, for the neuroprotective actions of this drug. We conclude that the histological outcome after administration of cerebral neuroprotectants should be assessed following long‐term survival. © 1995 Wiley‐Liss, Inc.
(Des‐tyr1)‐gamma‐endorphin (DTγE) in the treatment of depression: Double‐blind placebo‐controlled trial
Authors: Manchanda Rahul , Hirsch Steven
Published: May 2005

Preliminary evidence of a mood‐elevating effect for the endogenous neuropeptide, (des‐tyr1)‐gamma‐endorphin, was further investigated in a double‐blind placebo‐controlled trial over a period of 2 weeks. There were 10 patients in each group. Between‐group comparisons on the change in scores by day 14 were non‐significant. There was, however, a significant reduction (p = 0.05, two‐tailed) of scores on the Montgomery Asberg Depression Rating Scale and the anxious‐depression subscale of the BPRS in the endorphin group. It is recommended that the trial be conducted in a larger sample for definitive results.
A double‐blind comparative trial of remoxipride and haloperidol in the treatment of schizophrenia
Authors: Deo R. , Soni S. , Rastogi S. C. , Levine S. , Plant I. , Edwards J. Guy , Mitchell M. J. , Chanas A.
Published: May 2005

A multicentre parallel group study was carried out to compare the efficacy and safety of remoxipride, a new antipsychotic drug, with haloperidol in the treatment of acute schizophrenia. Patients were randomly assigned to the two groups and assessments were made under double‐blind conditions. Treatment was preceded by a washout period and lasted 6 weeks. Eighty‐nine consecutively admitted men and women meeting the Research Diagnostic Criteria for schizophrenia in an acute phase of the illness were treated with remoxipride 75–300 mg b.d. or haloperidol 5–20 mg b.d. The main assessments were changes in scores on the Brief Psychiatric Rating Scale, Krawiecka Rating Scale and Clinical Global Impression. Both neuroleptics produced clinical improvement but there were no significant differences in overall efficacy measurements between the two drugs. There were relatively few unwanted side‐effects. There were significantly less extra‐pyramidal symptoms and blurred vision with remoxipride, and less constipation with haloperidol. The results indicate that remoxipride is an effective antipsychotic drug with a low incidence of extrapyramidal side‐effects.
Age and anxiety: Increased anxiety, decreased anxiolytic, but enhanced sedative, response to chlordiazepoxide in old rats
Authors: File S. E.
Published: May 2005

The effects of chlordiazepoxide (7.5 mg/ kg) were assessed on the performance of young (3 months) and old (12 months) hooded Lister rats in the elevated plus‐maze test of anxiety. In young animals chlordiazepoxide significantly increased the percentage of entries onto open arms and the percentage of time spent on the open arms of the plus‐maze, measures that reflect its anxiolytic action. In the young animals this dose of chlordiazepoxide did not change the total number of arm entries, a measure that reflects its sedative action. However, in the old animals the only significant effect was a reduction in total arm entries. The effects of ageing on performance in the plus‐maze was assessed by testing rats at 3, 6, 9 and 12 months of age. Between 9 and 12 months the rats showed a significant decrease in the percentage of entries onto open arms and in the percentage of time spent on the open arms, indicating an increase in this measure of anxiety. Thus it seems that old rats might have an increase in their baseline measures of anxiety, coupled with a reduced anxiolytic response to benzodiazepines.
Tyramine‐Induced cardiac arrhythmias
Authors: Tiller J. W. G. , Maguire K. P. , Davies B. M. , Dowling J. T. , Tung L. H. , Rand M. J.
Published: May 2005

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug‐free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase‐A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low‐tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.
High‐dose anabolic steroids in strength athletes: Effects upon hostility and aggression
Authors: Choi P. Y. L. , Parrott A. C. , Cowan D.
Published: May 2005

Six male strength athletes, three illicit anabolic steroid users and three non‐steroid users were monitored over several months as they underwent normal training and competition routines. Subjects completed the Profile of Mood States (POMS) questionnaire, Buss‐Durke Hostility Inventory and the Rosenweig Picture Frustration Test on four occasions: two on‐drug periods and two off‐drug periods for the steroid users and equivalent test periods for the non‐users. Steroid presence was monitored objectively by gas chromatography coupled to mass spectrometry. Whilst those drugs declared by the athletes were confirmed in the “on‐drug” samples and most of the “off‐drug” samples, clear steroid traces were apparent in some supposed off‐drug sessions. This complicated data interpretation and may partially explain why steroid users were significantly more hostile and aggressive at all times compared to the non‐users. Despite this, self‐rated aggression did increase significantly in steroid users during their acknowledged on‐drug periods. Multiple drug use or “stacking” in particular caused severe hostility/aggression; one steroid user also admitted to attempted murder during a previous steroid‐taking phase.
Effect of hydroxyzine on attention and memory
Authors: De Brabander A. , Deberdt W.
Published: May 2005

A single intake of hydroxyzine 50 mg was compared to placebo, with lorazepam 2 mg as a verum, in a double‐blind, triple‐crossover trial. Each of the nine volunteers was tested on three different days, once under each condition. At 2‐h after drug intake all volunteers were assessed or reassessed for attention, immediate and delayed (30 min) memory, cognitive ability and subjective feelings of anxiety and fatigue. While hydroxyzine 50 mg and lorazepam 2 mg produced a comparable level of sedation, only hydroxyzine preserved memory and attention. The testing methods were sufficiently sensitive to demonstrate clear deficiencies in attention and short‐term and long‐term memory with lorazepam. Subjects became some what stressed under both sedative treatments because they feared losing their cognitive abilities. Subjects had fewer complaints under hydroxyzine than under lorazepam.
Effect of ceruletide on microvibration in schizophrenics
Authors: Nishikawa T. , Kuwahara H. , Tsuda A. , Tanaka M. , Koga I. , Uchida Y.
Published: May 2005

Ceruletide, a potent analogue of cholecystokinin, was administered by injection to eight schizophrenics treated with neuroleptics. We examined the dose–response effect on microvibration (MV) recorded from the chin of these patients. After 15 min of bed rest, MV was recorded for 5 min as a control recording. Subsequently, saline or ceruletide, at a dose of either 0.4 m̈g/kg or at 0.8 m̈g/kg, was injected according to a Latin square design with an interval of 4 weeks for washing out the drug effect and MV was recorded for 30 min. MV data obtained were subjected to the fast Fourier transform and an average power spectrum was computed. A three‐way analysis of variance for these data was performed upon dose‐effect, time‐effect after treatment, and band‐effect of the average power spectrum. The present results were similar to previous findings which had revealed effects of ceruletide on tardive dyskinesia symptoms, namely, the effects of ceruletide on MV were different according to the subjects (three cases: facilitation followed by inhibition, three cases: inhibition, two cases: no effects). The dose‐response curve of ceruletide appears to be linear in some cases and an inverted U‐shape in other cases. Present findings showed small doses of systemically administered ceruletide would modify muscle tonus of schizophrenics under chronic treatment of neuroleptics, and provided further reason for the therapeutic drug of tardive dyskinesia.
Comparison of mianserin and dothiepin treatment on the serotonergic system in depressed patients
Authors: Butler J. , Leonard B. E.
Published: May 2005

Depressed patients showed a decreased 5‐HT uptake rate and aggregation response and increased platelet ketanserin binding, compared to normal controls. Five weeks treatment with either mianserin or dothiepin improved the biochemical parameters in the patients, although the parameters still had not returned to control levels. There was no difference between the biochemical markers in the mianserin and dothiepin groups at any time during the study.
Effects of estazolam and triazolam on transient insomnia associated with phase‐shifted sleep
Authors: Schweitzer P. K. , Koshorek G. , Muehlbach M. J. , Morris D. D. , Roehrs T. , Walsh J. K. , Roth T.
Published: May 2005

Forty‐eight healthy volunteers with a normal sleep/wake history participated in a two‐centre, double‐blind, parallel group study comparing the effects of estazolam 2.0 mg, triazolam 0.25 mg, and placebo on sleep, performance and alertness following 180 degree reversal in sleep/wake schedule. Sleep‐phase reversal produced decreased sleep time, primarily during the last 2 hours of the sleep period. Estazolam prevented this transient insomnia by maintaining sleep in the latter part of the sleep period. Triazolam did not significantly change total sleep time, which was intermediate between that of the estazolam and placebo groups. Neither active compound produced significant effects on subsequent performance or alertness.
The effects of clobazam on critical flicker fusion threshold and symptomatology during the menstrual cycle
Authors: Dye Louise , Hindmarch Ian
Published: May 2005

The effects of clobazam on critical flicker fusion threshold (CFFT) and menstrual cycle‐related symptomatology were examined in a double‐blind placebo‐controlled study of 11 normally cycling women. Clobazam 10 mg or placebo was administered in two doses, the evening before and the morning of testing at four points in the menstrual cycle (days 7, 14, 21 and 26). Subjects were tested on CFFT and completed the Menstrual Distress Questionnaire (MDQ) and the Premenstrual Mood Index (PMI). Results showed that clobazam did not disrupt the menstrual cycle rhythm in CFFT, which accords with the non‐sedative nature of this drug. The lack of effect of clobazam on subjective indices, Impaired Concentration and Behaviour Change of the MDQ confirms the lack of sedative effects. A general tendency, however, was observed for clobazam to reduce symptom reports on some other MDQ PMI scales in the first half of the cycle and to produce a subsequent exacerbation of symptoms in the second half of the cycle.
Fengabine in depression: A placebo‐controlled study of a GABA agonist
Authors: Paykel E. S. , van Woerkom A. E. , Walters D. E. , White W. , Mercer J.
Published: May 2005

A double‐blind controlled trial of Fengabine, a GABA agonist, against placebo was carried out in outpatient major depressives. Subjects were treated for up to 6 weeks with Fengabine three times daily using 900 mg daily in the first week and 1800 mg daily thereafter. A total of 49 subjects were included, of whom 32 completed 6 weeks. Efficacy analyses showed no evidence of superiority of active drug over placebo, and the two groups were closely comparable throughout the study. Fengabine was free of subjective side‐effects other than a small number of complaints of nausea and diarrhoea, and some ocurrence of bright yellow urine. There was a substantial incidence of raised liver enzymes: 44 per cent of patients on Fengabine developed some de novo elevation, necessitating early termination of the study. The findings did not support any therapeutic value for this group of GABA agonists in depression.
Modulation of mouse brain dopamine, serotonin and metabolites by methionine: Implications for schizophrenia and genetics
Authors: Messiha F. S.
Published: May 2005

The effect of methionine, an essential amino acid, on brain regional distribution of dopamine, serotinin and major acidic metabolites was studied in two genetically different strains of mice. These were the inbred albino BALB/C and the black C57BL/6 mouse strains. The later strain was more sensitive than the former mouse strain to the methionine treatment. This has been demonstrated by methionine‐produced change in dopamine metabolites in cerebellum, cortex and medulla regions, which suggests a decrease in dopamine turnover in the C57BL/6 mice. Conversely, methionine‐mediated changes in BALB/C mouse medullary region was suggestive of an increase in dopamine turnover. Little changes occurred in cerebral serotonin or 5‐hydroxyindoleacetic acid levels, except for an increased serotonin in C57BL/6 mouse midbrain region. The results suggest that methionine possesses CNS pharmacological property pertaining to dopamine, other than its well‐known action as a methyl donor in transmethylation processes, which is genotypic‐dependent. Alternatively, modulation of the monoamines by methionine may explain its antidepressant property and possible contribution to the pharmacological hypotheses relevant to the biology of schizophrenia.
Effects of acute and repeated doses of two muscle relaxants chlormezanone and thiocolchicoside, on vigilance and psychomotor performance of healthy volunteers
Authors: Patat A. , Klein M. J. , Surjus A. , Renault M. , Rezvani Y. , Granier J.
Published: May 2005

This was a randomized double blind, placebo‐controlled cross over study performed on 12 healthy female volunteers. It consisted of three treatment sessions of 7 days separated by a one week wash out period. The objectives of the study were to assess the sedative activity of 2 muscle relaxant drugs: chlormezanone (600 mg daily) and thiocolchicoside (16 mg daily) after a single oral administration and at steady state (day 7).

The drugs were administered orally, during each treatment period as 3 capsules daily for 7 days. Assessment criteria explored psychometric tests, body sway and subjective feeling rating scales. Chlormezanone induced objective disturbances of vigilance and concentration characterised by a decrease in the performance of an arithmetic calculation test and an increase in body sway area recorded in comparison with thiocolchicoside and placebo. These impairments were mainly marked on steady state. Most of the volunteers (10 over 12) complained of drowsiness throughout this treatment. Thiocolchicoside was devoided of any objective or subjective sedative side effect.
Effects of alcohol on serum fluphenazine levels in stable chronic schizophrenics
Authors: Soni S. D. , Bamrah J. S. , Krska J.
Published: May 2005

Seven chronic schizophrenic patients, stable for over 12 months on maintenance fluphenazine decanoate, were administered 40 g of alcohol orally soon after their regular injection. Blood samples for estimation of serum neuroleptic and prolactin levels were collected at various intervals over a 12 h period. The procedure was repeated at their next regular injection but without alcohol. It was found that alcohol ingestion produced a significant drop in both serum neuroleptic and prolactin levels which persisted during the study period.
The comparative psychopharmacology of 5HT reuptake inhibitors
Authors: Kerr J. S. , Sherwood N. , Hindmarch I.
Published: May 2005

The psychopharmacological profiles of the 5HT reuptake inhibitors sertraline, paroxetine, fluoxetine, fluvoxamine, Jouveinal (JO 1017) and zimeldine are described, and their relative behavioural toxicity ratings are compared. The pharmacodynamic activity of these drugs was assessed using a standardised test battery, including critical flicker fusion threshold (CFF), choice reaction time (CRT), tracking and subjective rating scales. The 5HT reuptake inhibitors were essentially neutral; indistinguishable from placebo on most of the measures. Paroxetine, sertraline and zimeldine produced an alerting effect as indicated by elevated CFF thresholds. The only drug which produced a consistently significant performance decrement with respect to placebo was the amitriptyline verum. These results hold true both for normal volunteers and for patients.
Amphetamine effects on recovery sleep following total sleep deprivation
Authors: Penetar D. M. , Sing H. C. , Thorne D. R. , Thomas M. L. , Fertig J. B. , Schelling A. S. D. , Sealock J. C. , Newhouse P. A. , Belenky G.
Published: May 2005

Normal, healthy adult males participated in a sleep deprivation study during which periodic assessments of mood, alertness, cognitive performance, and vital signs were made. After 48 hours of continuous wakefulness, placebo or d‐amphetamine (5, 10, 20 mg) was administered orally in a double‐blind fashion. Assessments continued for an additional 14 hours at which time the subjects were allowed to sleep. A significant difference in total sleep time was observed with the highest amphetamine group (20 mg) averaging 7·0 hours vs. 8·1 hours for the placebo group. The decrease in total sleep time was due largely to a significant decrease in REM time. The number of REM episodes was not affected by drug. Latency to the first REM episode was decreased by the 5 and 10 mg dose but unchanged by the 20 mg dose of amphetamine. Amphetamine's significant effects on total sleep time and other parameters more than 15 hours after administration indicate a prolonged drug effect.
Remoxipride in acute psychosis: Intramuscular followed by oral treatment compared to haloperidol, a doubleblind, multicenter trial
Authors: Kahn J‐P. , Laxenaire M. , Burnat G. , Albaret C. , Holm A‐C.
Published: May 2005

A double‐blind, randomized, multicentre study comparing the efficacy and safety of intramuscular (i.m.) remoxipride to that of i.m. haloperidol was undertaken in 119 psychotic patients (mean age: 37 ± 13.4 years). The study period was 1 week i.m., followed by 3 weeks of oral treatment. Dosage was 200–600 mg/day for remoxipride and 10–30 mg/day for haloperidol during i.m. and 150–600 mg/day for remoxipride and 10–40 mg/day for haloperidol during oral treatment. Both drugs produced marked clinical improvements during i.m. and oral treatment. During the i.m. week, the median Brief Psychiatric Rating Scale (BPRS) total score decreased from 51 to 34 in the remoxipride group and from 53 to 38 in the haloperidol group. Over the 4‐week treatment period, there was a significantly greater reduction in ‘some factors’ for remoxipride‐treated patients when compared to haloperidol‐treated patients. Somnolence was reported by 14% of haloperidol‐treated patients during i.m. treatment. Akathisia and tremor occurred significantly less in remoxipride‐treated patients as compared to haloperidol‐treated patients. Intramuscularly administered remoxipride is as effective as haloperidol in reducing acute phase psychotic symptoms, and is associated with fewer extrapyramidal symptoms.
Clinical sleep patterns in human immune virus infection
Authors: Wheatley David , Smith Kitty
Published: May 2005

Clinical sleep patterns were recorded in 45 HIV +ve patients, using a 5‐item questionnaire concerned with: sleep onset, nocturnal wakings, early morning awakening, duration of sleep and well‐being on final waking. These were quantified to give a total ‘insomnia score’ and compared to matched normal controls. Sleep was significantly worse in the HIV patients in relation to: delayed onset and early morning awakening (p < 0.5), nocturnal wakings and wellbeing on waking (p < 0.0001), although not significant for duration of sleep. The mean total score for the HIV patients was 3.8 and for the controls 2.1 (p < 0.0001). There was an almost significant correlation between insomnia score and duration HIV +ve (p = 0.055). AIDS status did not affect the results but the insomnia score was greater in the absence of anti‐viral chemotherapy (p = 0.052). In the controls insomnia severity almost correlated to stress (p = 0.052). The results showed that the HIV patients had significantly more sleep disturbance than the matched controls, with resultant implications for improving quality of life in this respect.
On the medico‐social aspects of khat (Catha edulis) chewing habit
Authors: Balint G. A. , Balint Erica E.
Published: May 2005

Regular consumption of khat from Catha edulis seriously affects the social and economic life of the subject and therefore is hazardous both to the individual and the community.

Increasing awareness of the prevalence of khat chewing, often together with other drugs such as alcohol and tobacco, it is essential to further assess the health and socio‐economic consequences of khat habituation in order to take further appropriate medical and social measures to limit its availability and use.
Pretask smoking and smoking during a task: Effects on cognitive performance, puffing behavior, physiological and subjective parameters
Authors: Hasenfratz M. , Bättig K.
Published: May 2005

Twenty female regular smokers participated in four experimental sessions, each of which involved performing a rapid information processing task (RIP) twice. According to a 2 × 2 cross‐over design the subjects were allowed to either real or sham smoke a single habitual cigarette between the two RIP trials and to real or sham smoke ad libitum during the second RIP trial. RIP performance was significantly better when the smokers were allowed to smoke during the task. On the other hand, the improvement after pretask smoking failed to reach significance. The puffing intervals were similar for real and sham smoking during rest but significantly longer with real than with sham smoking during the task. The increases in electrocortical and cardiovascular arousal as well as the subjective effects were similar for pretask and task smoking. After pretask smoking these effects vanished for the subsequent task period, whereas they were maintained but not further increased when pretask smoking was followed by task smoking. It was concluded that mental performance was increased but overarousal was avoided by accurate nicotine titration during the RIP task.
Videotaped reliability in a multicenter collaborative investigation of divalproex sodium for the treatment of mania
Authors: Altman Edward G. , Peterson James L. , Hedeker Donald R. , Janicak Philip G. , Davis John M.
Published: May 2005

This study describes the procedures used to establish videotaped inter‐rater reliability in a multicenter study investigating the clinical efficacy of divalproex sodium for the treatment of acute mania. A total of 46 raters from 10 centers viewed and rated five videotaped diagnostic patients interviews using a modified SADS and SADS‐C. Raters also viewed a follow‐up videotaped interview at the midpoint of the study. Raters rated the quality of each interview for its teaching potential. Agreement among raters within study sites was estimated by the intraclass correlation coefficient. Results demonstrated significant agreement among raters within study centers at baseline and follow‐up for both the SADS and SADS‐C.
Non‐cognitive disturbances in alzheimer's disease
Authors: Lawlor Brian A.
Published: May 2005

Although the hallmark of Alzheimer's disease (AD) is memory loss, behavioural and psychiatric disturbances are common and often pose the greatest problems for carers and patients. Modifying behavioural disturbance in AD sufferers can delay institutionalization and improve the quality of life of patient and caregiver. The failure to appreciate the importance of the behavioural and psychiatric disturbances in AD and their impact on the care of patients in the community has resulted in a dearth of services, resources and research into the management of the non‐cognitive aspects of this illness.
Effects of single and multiple doses of a new reversible MAO‐A inhibitor, befloxatone, on psychomotor performance and memory in healthy subjects
Authors: Patat A. , Gandon J. M. , Durrieu G. , Le Coz F. , Curet O. , Cimarosti I. , Allain H.
Published: May 2005

The effects on memory, psychomotor performance and mood of two dosage regimens of befloxatone, a new reversible and selective MAO‐A inhibitor were assessed in a randomized, double‐blind, cross‐over, placebo‐controlled study involving 12 healthy young male volunteers. Befloxatone and a placebo were orally administered as single (5 and 10 mg) and repeated doses (10 mg once daily and 5 mg twice daily) at one week wash‐out intervals. Objective tests evaluated both memory (working memory, immediate and delayed free recall of a word list, dual coding and faces recognition) and vigilance continuous performance task (CPT), and digit symbol substitution (DSST). Subjective mood and sleep were assessed using visual analogue scales and the Leeds Sleep Evaluation Questionnaire. Statistical analysis was conducted using an ANOVA with pairwise comparisons using the Student Newman Keuls procedure.

Both dosage regimens of befloxatone (10 mg once daily or 5 mg twice daily) were free of any detrimental effect on vigilance (CPT) and information processing (DSST) and did not significantly disrupt short‐ and long‐term memory (working memory, free recall of words, dual coding and faces recognition). In addition, no subjective sedation or sleep disturbances were recorded.

In conclusion, this study gives no evidence to suggest that befloxatone, at a daily dose which shows potent MAO‐A inhibition, has any sedative or amnestic properties likely to interfere with the activities of everyday‐life in young subjects and therefore may be safely administered in depressed outpatients.
Paroxetine induced withdrawal effects
Authors: Koopowitz L. F. , Berk M.
Published: May 2005

Withdrawal reactions following discontinuation of tricyclic antidepressants and short acting selective serotonin reuptake inhibitors (SSRI) have been reported. We describe three cases of paroxetine induced withdrawal effects.
Org 3770 versus amitriptyline: A 6‐week randomized double‐blind multicentre trial in hospitalized depressed patients
Authors: Zivkov Milana , De Jongh Geoff D.
Published: May 2005

Following a placebo washout period of 3–7 days, 251 hospitalized patients with a major depressive episode (DSM III and RDC criteria) were treated with either Org 3770 (20–60 mg/day) or amitriptyline (75–225 mg/day) for six consecutive weeks in this randomized, double‐blind, multicentre study. Forty‐one patients (19 Org 3770, 22 amitriptyline) withdrew before completion of the 6‐week active treatment period. In both groups, the main reason for withdrawal was lack of efficacy. However, fewer patients in the Org 3770 group than in the amitriptyline group withdrew as a result of adverse events (one and three patients, respectively). The severity of depressive symptoms and general psychopathology, as assessed by HPRSD (total and factors) and BPRS scales, improved to the same extent after 6 weeks' treatment with Org 3770 and amitriptyline. Similar improvement in global functioning, as assessed by GAS scale, was observed in both treatment groups. There were no statistically significant differences between the two treatments on all scales used. Dry mouth and sweating were reported significantly more often in the amitriptyline group. Other adverse events, such as constipation, dizziness, tremor and muscle weakness, occurred more frequently in the amitriptyline‐treated patients as well. The results of this study indicate that Org 3770 has similar antidepressant efficacy to amitriptyline and a more favourable tolerability profile in patients with major depression.
A multicentre double‐blind placebo‐controlled study investigating the anxiolytic efficacy of hydroxyzine in patients with generalized anxiety
Authors: Darcis T. , Ferreri M. , Natens J. , Burtin B. , Deram P.
Published: May 2005

The efficacy of hydroxyzine was investigated in 110 patients suffering from generalized anxiety, in a double‐blind placebo controlled multicentre study. Oral hydroxyzine 50mg/day for four weeks significantly improved standard measurements of anxiety compared with placebo control. These improvements were seen from the end of the first week of treatment and were maintained throughout the study; there was no rebound effect after cessation of therapy. The most commonly reported adverse effect in both active and placebo treatment groups was a transient sleepiness. We conclude that hydroxyzine is an effective and well‐tolerated treatment for generalized anxiety.
Efficacy of venlafaxine treatment in depressed patients with psychomotor retardation or agitation: A metaanalysis
Authors: Entsuah R. , Upton G. V. , Rudolph R.
Published: May 2005

A meta‐analysis was performed to assess the effectiveness of the novel antidepressant venlafaxine in depressed patients with psychomotor retardation and/or agitation [respective baseline item score greater than zero on the Hamilton Rating Scale for Depression (HAM‐D)]. Data from five comparable placebo‐controlled double‐blind studies (n = 1122) were analysed; in two of them venlafaxine was also compared with imipramine. Separate analyses were performed on data from psychomotor retarded and agitated patients by using a one‐way analysis of covariance (HAM‐D total score during therapy, dependent variable; baseline HAM‐D total score, covariate; therapy, factor). The overall pool of venlafaxine‐treated patients showed a significantly greater decline in total HAM‐D score than did the placebo‐treated patients. Venlafaxine‐treated patients with retardation showed a significantly greater decline in total HAM‐D scores than did placebo‐ and imipramine‐treated patients, starting at weeks 3 and 4, respectively. Venlafaxine‐treated patients with agitation showed a significantly greater decline in total HAM‐D scores than did placebo‐and imipramine‐treated patients, starting at weeks 2 and 1, respectively. In conclusion, venlafaxine is effective in depressed patients whether or not they have symptoms of psychomotor retardation or agitation.
A pilot, open study on the treatment of refractory schizophrenia with risperidone and clozapine
Authors: Cavallaro Roberto , Colombo Cristina , Smeraldi Enrico
Published: May 2005

The aim of this report is to show the results of a pilot, open label treatment programme for resistant schizophrenics in which risperidone was used before clozapine. Thirteen DSM III R, drug resistant schizophrenics were treated with risperidone p.o. at doses up to 16 mg/day for three months. Clinical assessment was performed before and after 1, 2 and 3 months of treatment by means of the Brief Psychiatric Rating Scale (BPRS) and of the Scales for the Assessment of Positive and Negative Symptoms of Schizophrenia. Non‐responders to risperidone were then treated with clozapine (up to 600 mg/day) for the next month.

Seven patients responded to risperidone (improvement over 20 per cent in each rating scale, BPRS total score below 35), While five risperidone non‐responders or partial responders improved dramatically after following clozapine tretment. Results suggest that heterogeneity in response to atypical antipsychotics may overshadow a heterogeneity in underlying biological factors.
Aerophagia: A neuroleptic‐associated tardive syndrome?
Authors: Hayashi Teruo , Nishikawa Tadashi , Kado Kazuo , Koga Itsuyuki , Uchida Yasunori , Yamawaki Shigeto
Published: May 2005

Some cases suggestive of a tardive dyskinesia (TD)‐induced esophageal movement disorder have been reported. We represent a patient with severe orofacial dyskinesia, an oesophageal movement disorder, and aerophagia following long‐term neuroleptic treatment. This 40‐year‐old mentally retarded man showed signs of oral dyskinesia over 20 years ago, with extension to his limbs and trunk within the last 5 years. He also demonstrated noisy air gulping every several seconds. An abdominal radiograph revealed a big magenblase and dilatated, air‐filled segments of large and small intestine without a niveaus. Oesophageal contrastradiography revealed evidence of an oral dyskinesia involving the esophageal musculature and a dilated oesophagus (maximal width: 4·5 cm). Although the oesophageal dilatation was similar to that in patients with a spindle type of achalasia, the oesophageal‐cardio junction was sometimes open completely, differing from conditions associated with achalasia. A polygraphic study revealed frequent high‐amplitude bursts of microvibration, concurrent with the gulping. The signs of aerophagia and laryngeal dyskinesia decreased 6 days following clonazepam administration. Thus, we suggested that tardive dyskinesia is associated with the laryngeal and oesophageal‐induced aerophagia. This is the first report of aerophagia associated with neuroleptic‐induced tardive syndrome.
Transcranial magnetic stimulation (TMS) in the treatment of major depression — a pilot study
Authors: Kolbinger Hans Martin , Höflich Gereon , Hufnagel Andreas , Müller Hans‐Jürgen , Kasper Siegfried
Published: May 2005

Transcranial magnetic stimulation (TMS) is a diagnostic method well established in neurology. As some effects of TMS are similar to those of electroconvulsive therapy (ECT), we looked for an antidepressant efficacy of TMS in a semi‐blinded monocentric pilot study. Fifteen patients with Major Depression (DSM‐III‐R) were included. Ten patients were randomized into two groups and treated with 250 transcranial magnetic stimuli/session for five consecutive days. Stimulus intensity in the two groups was motoric threshold ± 0.3 tesla respectively. Five patients received placebo stimulation in a similar setting. As assessed by the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI), and the Adjective Mood Scale of von Zerssen (Bf‐S/Bf‐S'), there was an improvement of depressive symptoms in both verum groups, more pronounced in the ‘stimulation below threshold’ group. Patients in the placebo group did not benefit from stimulation. Our data suggest that TMS might indeed have a relevant antidepressive efficacy.
Ethanol‐Induced CNS depression and divided attention
Authors: Millar S. A. , Duncan L. , Tiplady Brian
Published: May 2005

Subject performed a divided attention task in which they detected occurrences of a target letter in a stimulus figure which was a large letter made up of an array of small letters. Subjects pressed one button if the large letter was the target, another if the small letters were the target.

Performance on this task was compared to other attention and psychomotor tasks in a three‐way randomized crossover study comparing two doses of alcohol with placebo in 12 healthy volunteers (six male, six female, aged 19–41). The higher dose of alcohol produced blood concentrations of 43 mg/100 ml, the lower dose 16 mg/100 ml.

Subjects reported themselves significantly more drunk on both doses of alcohol than on placebo, showed poorer long‐term recall on the Buschke selective reminding task than on placebo, and made more errors on a letter cancellation task. They performed letter cancellation faster, however. No significant effects were seen on the divided attention or continuous attention tasks, though continuous attention showed a trend towards impairment.

These results suggest that the greater sensitivity showed by some multiple task combinations to low doses of drugs such as alcohol is not due to divided attention as such, but results from some aspect of task combination. The coupling of increased errors but increased speed on letter cancellation has obvious implications for the interpretation of the effects of alcohol on complex real‐life tasks such as driving.
Digit letter substitution test (DLST) as an alternative to digit symbol substitution test (DSST)
Authors: Natu M. V. , Agarwal A. K.
Published: May 2005

In the present study, a modification has been suggested in DSST to overcome some of its demerits. In the new test, DLST, the symbols have been substituted by letters from the English alphabet. The new test seems to be stable, valid and sensitive. It has similar basic structure and sensitivity with added advantage of better understanding by subjects, easy preparation of parallel work sheets and faster evaluation. We propose that the new test may serve as a good alternative to DSST.