Behavioural effects of electrolytic and 6-hydroxydopamine lesions of the accumbens and caudate-putamen nuclei.

Selective bilateral destruction of dopaminergic neuronal terminals in the accumbens nuclei with 6-hydroxydopamine reduced spontaneous and amphetamine-induced locomotor and exploratory behaviour and sniffing activity; amphetamine-induced stereotyped behaviour appeared to be mildly potentiated. Similarly induced bilateral destruction of dopaminergic nerve endings in the caudate-putamen reduced spontaneous activity; amphetamine-induced stereotyped behaviour was abolished. Some animals with severe degrees of neostriatal dopamine depletion were completely unresponsive to amphetamine, apart from intense sniffing activity. Bilateral electrolytic lesions of the accumbens nuclei did not alter spontaneous or amphetamine-induced activity.

Behavioural responses to stereotactically controlled injections of monoamine neurotransmitters into the accumbens and caudate-putamen nuclei.

Bilateral stereotactically-controlled injections of dopamine (5--50 micrograms of the hydrochloride salt) into the nucleus accumbens of nialamide-pretreated rats induced a marked stimulation of exploratory and locomotor activity, accompanied by intense sniffing and rearing. Conversely, bilateral injection of domapine (12.5--50 micrograms of the hydrochloride salt) into the caudate-putamen induced intense stereotyped activity which was dose-related. Both responses were blocked by IP haloperidol. Bilateral injection of noradrenaline (50 micrograms of the hydrochloride salt) into the accumbens nuclei did not produce any particular behavioural changes. The same injection into the caudate-putamen led to a moderate stimulation of stereotyped activity. Bilateral injection of 5-HT (50 micrograms of the bimaleinate salt) into the accumbens nuclei induced a moderate locomotor activity with some hole-dipping activity and sniffing; these behaviours were incoordinated and indecisive. The same injections into the caudate-putamen led to a moderate stimulation of locomotor activity and hole-dipping which was predominantly 'stereotyped' in character; on visual observation no other striking abnormalities were noted.

An automated method for studying exploratory and stereotyped behaviour in rats.

A technique is described for studying exploratory as well as stereotyped behaviour in rats using an automated hole-board. Both visual and automated recordings can be employed using the technique. Hole dipping is monitored automatically using an infra-red detector system. Repetitive patterns of hole-dipping are used as parameters of stereotyped behaviour while the more random patterns of hole-dipping are used as parameters of exploration. There was a high significant correlation between the records of hole-dipping behaviour as recorded visually and automatically. There was also a high significant correlation between the measures of repetitiveness/randomness of hole-dipping behaviour from automatic and visual recordings. The pattern and levels of hole-dipping conformed with expectations both as regards changes with time and with increasing doses of dl-amphetamine.

The effects of psychotropic drugs on exploratory and stereotyped behaviour of rats studied on a hole-board.

Exploratory and stereotyped behaviour of Male Wistar rats was studied on a hole-board. The two forms of behaviour were differentiated according to the pattern of hole-dipping activity. Increasing doses of dl-amphetamine stimulated both forms of behaviour with stereotyped behaviour becoming predominant particularly at the higher dose levels. At the highest dose of amphetamine used (16 mg/kg) a gradual transition from exploratory to stereotyped behaviour was observed with time. As the drug wore off this transition was reversed. Haloperitol at a dosage of 0.1 and 0.05 mg/kg blocked the response to a high dose of amphetamine whereas a lower dose (0.02 mg/kg) blocked the stereotyped response to amphetamine while some exploratory behaviour still took place. Apomorphine inhibited hole-dipping but at lower doses another form of exploratory behaviour was induced, this behaviour becoming stereotyped as the dose was increased. It is concluded that there is a close relationship between exploratory and stereotyped behaviours. Monoamine systems appear to play a significant role in the regulation of both forms of behaviour.

The effect of clomipramine treatment on plasma lipoproteins and high density lipoprotein subfractions in healthy subjects.

The effect of clomipramine on plasma lipoproteins, including high density lipoprotein (HDL) subfractions in five healthy males was investigated. The concentrations of total plasma cholesterol and low density lipoprotein cholesterol decreased slightly while that of total HDL-cholesterol showed a small increase, giving a decrease (p less than 0.05) in the ratio of total plasma cholesterol to HDL-cholesterol. The level of HDL2-cholesterol increased (p less than 0.01) with clomipramine treatment while there was no significant change in the concentration of HDL3-cholesterol. Gradient gel electrophoresis showed that administration of the drug was associated with an increase in the relative concentration of HDL2a as well as of HDL2b and a decrease in that of HDL3b/3c. The plasma concentration of apolipoprotein (Apo) A-I showed a small but insignificant increase. These changes in lipoprotein profile are characteristic of those associated with a decrease in coronary risk.

Role of doctors in the prevention of suicide: the final consultation.

BACKGROUND: It is generally assumed that people committing suicide see their doctor shortly before their death, and consequently that enhancing doctors' psychiatric knowledge and interview skills might help prevent some suicides. AIM: A study was undertaken to determine the nature and timing of final contacts with medical practitioners by people committing suicide. METHOD: Adults dying by suicide in Scotland during 1988-89 were identified by the General Register Office for Scotland and their primary care case notes studied. RESULTS: Within this national sample, medical contact near to the time of the suicidal act was rare, except for those individuals who had a previous psychiatric history. CONCLUSION: These data suggest that medical practitioners, particularly those working in primary care, are not failing to detect and intervene in significant numbers of preventable suicides. Consequently, the likelihood of implementing successful suicide prevention strategies based within primary care is open to question. Greater awareness of the risk of eventual suicide in those with a previous history of psychiatric disorder may contribute to any future reduction in suicide rates.

Relation between cognitive impairment and early death in the elderly.

STUDY OBJECTIVE: To study the association between cognitive impairment and early death in elderly patients living in the community. DESIGN: Case-control study of 410 patients assessed by the mental status questionnaire and followed up after three years. SETTING: A general practice in Inverurie, Aberdeenshire, with 14,000 patients. PATIENTS: 205 Patients aged greater than or equal to 65 with cognitive impairment according to the mental status questionnaire (score less than or equal to 8) and 205 patients scoring greater than 8 on the questionnaire matched for age and sex. MAIN OUTCOME MEASURE: Death. RESULTS: The relative risk of death in the cognitively impaired patients overall was 3.5. Those patients who scored less than or equal to 7 on the mental status questionnaire were five times more likely to die than their controls. There was no difference in risk of death between those with severe or moderate cognitive impairment. CONCLUSIONS: Cognitive impairment is associated with early death.

The active transport of 5-hydroxyindol-3-ylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid from a recirculatory perfusion system of the cerebral ventricles of the unanaesthetized dog.

1. An operation on dogs for the implantation of guide tubes to the lateral ventricle and cisterna magna and a method whereby the ventricular space can be repeatedly perfused in conscious and unrestrained animals are described.2. The characteristics of a recirculatory perfusion system were examined and the bulk formation and absorption of cerebrospinal fluid and the volume of the ventricular space perfused were derived from the concentrations achieved during the infusion of inulin into the system.3. 5-hydroxyindol-3-ylacetic acid (5-HIAA), the acid metabolite of 5-hydroxytryptamine, and 3-methoxy-4-hydroxyphenylacetic acid (HVA), the main acid metabolite of dopamine, were demonstrated to be mainly removed from cerebrospinal fluid (c.s.f.) by an active transport system localized in the region of the fourth ventricle.4. It was possible to inhibit the active transport of these acids from cerebrospinal fluid by pre-treating the dogs with probenecid.

Suicide in Scotland 1988-1989. Psychiatric and physical morbidity according to primary care case notes.

BACKGROUND: The aim was to identify the amount of psychiatric and physical morbidity identified in suicide victims prior to death. METHOD: A survey was made of primary care records of Scottish suicide victims in the years 1988 and 1989. RESULTS: Less morbidity was encountered than in previous studies. Single persons and persons from lower socio-economic groups were less likely to have a diagnosis of depression. No association was found between physical and psychiatric morbidity. Depressed single persons and depressed persons from lower socio-economic groups were less likely to receive antidepressants. GPs prescribed lower dosages of antidepressants than psychiatrists. Patients receiving antidepressants were more likely to die by drug overdose. CONCLUSIONS: There are groups in whom depression may be being overlooked and others in whom depression could be treated more vigorously. There are risks in prescribing antidepressants which are potentially fatal in overdose.

Zimelidine and amitriptyline in the treatment of depressive illness in general practice.

Depressive patients seen at hospital clinics are likely to be unrepresentative in terms of treatment response. In this study patients were always seen at their general practitioners' surgeries for assessment by specialists after selection as being in need of antidepressant treatment. The Research Diagnostic Criteria for major or minor depressive illness and a Hamilton Depression (Ham-D) score of at least 10 were required for inclusion, using the Present State Examination as a basis for interview. Patients were seen at weekly intervals, alternatively by practitioner and assessor for further Ham-D ratings, completion of the Kellner Sheffield Self-Rating test (KSSRT), event record and side effect checklist. Patients were randomly and blindly allocated to either zimelidine or amitriptyline dispensed identically at dosages of 100 mg and 75 mg at night, rising to 200 mg and 150 mg after two weeks. At four weeks there was no significant difference between the improvement found with zimelidine and amitriptyline or either the Ham-D or the KSSRT. Amitriptyline patients tended to gain and zimelidine patients to lose weight; difference significant. Other amitriptyline side effects were not found in those taking zimelidine, the latter tending to suffer diarrhoea. Preliminary analysis shows no relationship between clinical response and plasma level of either compound.

The mental health of elderly couples. I. The effects of a cognitively impaired spouse.

In a general practice population, 274 elderly married couples completed the Mental Status Questionnaire (MSQ), the 60-item General Health Questionnaire (GHQ) and the Leeds General Scales for the Self-assessment of Depression and Anxiety. The only relationship detected between cognitive impairment on the MSQ and psychiatric morbidity in the partner was a fairly weak negative correlation between the wives' MSQ and the Leeds Depression score of their husbands. These findings differ from those of previous studies, which have found high rates of psychiatric morbidity in the relatives of demented patients, and the possible reasons for these differences are discussed. Most importantly, other studies have involved the relatives of patients referred to psychiatric services, and these families may be quite different from those in which the demented relative is not referred to a psychiatrist.

[NMR imaging in dementia states. A diagnostic and quantitative study]. / NMR-imaging in Demenzzuständen. Eine diagnostische und quantitative studie.

Spin lattic relaxation times (T1) and proton density derived from proton nuclear magnetic resonance imaging data are measured in elderly patients with senile dementia of Alzheimer type (SDAT) and multi infarct dementia (MID) and the results compared with elderly controls. T1 values of the cerebral white matter are increased in the dementia groups and there is a statistical correlation with severity. Patients with SDAT have significantly differing proton density measures in cerebral white matter from those with MID. The potential value of these results are discussed together with the possible application to identify regional areas of damage.

Nuclear magnetic resonance (NMR). II. Imaging in dementia.

Proton NMR imaging of the brain is rapidly becoming established as a useful investigative tool in medicine. This paper examines the usefulness of the NMR parameters--spin-lattice relaxation time (T1) and proton density (PD)--in differentiating groups of patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) from each other, and from elderly controls. T1 values increase with severity of dementia. NMR parameters may also be of use in localising regions of brain damage.

Cognitive evaluation following NMR imaging of the brain.

Nuclear magnetic resonance imaging of the brain will soon be a standard neuroradiological investigation. Previous work has indicated that this is a safe procedure. Tests which measure various aspects of cognition were performed on volunteer subjects before and after (medium and short term) NMR brain imaging and indicate that deterioration did not occur.

The treatment of depression in general practice: a comparison of L-tryptophan, amitriptyline, and a combination of L-tryptophan and amitriptyline with placebo.

One hundred and fifteen patients from 5 general practices participated in a 12-week, double-blind study comparing L-tryptophan, amitriptyline, L-tryptophan-amitriptyline combination and placebo in the treatment of depression. Analysis of total score on the Hamilton Depression Scale and a global rating of depression showed that all 3 active treatments were more effective than placebo. Significantly more patients were withdrawn as treatment failures in the placebo group compared with the active treatment groups. Side-effects necessitated withdrawal of more patients from the amitriptyline group than from the other active treatment groups, but this difference was not significant. Plasma amitriptyline and nortriptyline levels were similar in the amitriptyline and combined treatment groups. Standard haematological and biochemical profiles did not alter significantly in any group, but mean heart rate was significantly increased in patients receiving amitriptyline. There was no change in free or total plasma tryptophan concentration with treatment or on remission of symptoms.

Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography.

BACKGROUND: Diagnostic classes (derived from CATEGO) can be correlated with regional brain metabolism in patients with major psychiatric disorders. METHOD: Seventeen patients with schizophrenia, 15 with mania, 10 with depression and 10 healthy Volunteers were examined with positron emission tomography (PET) and 18F-labelled fluorodeoxyglucose, as a marker for glucose metabolism. The number of possible comparisons of regions of interest was reduced by principal-components analysis, and differences in factor scores were determined between diagnostic groups. RESULTS: Four independent factors, representing distributed brain systems, emerged: an anterior-posterior (1), a left-right temporal (2), a temporofrontal (3), and a mediofrontal (4) system, of which (1), (2) and (3) were abnormal in schizophrenia, (1) and (2) in mania, and (1) in depression. CONCLUSIONS: Abnormal patterns of metabolism could be detected, in decreasing order, in schizophrenia, mania and depression. Some of these abnormalities are likely to be due to medication, but others will be associated with structural or functional abnormalities of the frontolimbic system in the diagnostic groups.

[Relation between Parkinson disease and dementia conditions studied with proton NMR imaging parameters]. / Das Verhältnis zwischen M. Parkinson und Demenzzuständen untersucht mit Hilfe von Protonen-NMR-Abbildungsparametern.

The value of the spin lattice relaxation time (T1) obtained during nuclear magnetic resonance imaging of the brain in patients with Idiopathic Parkinson's disease with and without dementia is studied. T1 increases significantly in the basal ganglia and cerebral white matter of the demented and nondemented groups. T1 of the cerebral white matter correlates with the severity of dementia.