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Biomedical subjects

A Longden

Publications and source records attributed to A Longden.

At least 19 recordsLinked to original sources
PubMed1979

Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings.

Dopamine and its metabolites homovanillic acid and dihydroxyphenylacetic acid, noradrenaline, serotonin and its metabolite 5-hydroxyindoleacetic acid, and tryptophan and its metabolite kynurenine have been assayed in 9 schizophrenic and 10 control brains, together with the monoamine-related enzymes tyrosine hydroxylase monoamine oxidase, dopamine-beta-hydroxylase, and catechol-o-methyl-transferase. In schizophrenic brains dopamine, noradrenaline and serotonin were significantly increased in some areas of corpus striatum, but there were no significant changes in enzyme activity or monoamine metabolite concentrations in any of the brain areas examined. The findings are not consistent with theories that serotonin or noradrenaline stores are grossly depleted or noradrenaline neurones have degenerated, or that monoamine oxidase activity is abnormal, in schizophrenia, and provide no direct support for the hypothesis that dopamine neurones are overactive.

Aged↗
PubMed1978

The activities of brain dopamine-beta-hydroxylase and catechol-O-methyl transferase in schizophrenics and controls.

It has been suggested that deterioration of central noradrenergic pathways may be responsible for the production of certain schizophrenic symptoms, and that such a degeneration might be reflected in lowered dopamine-beta-hydroxylase (DBH) activity in the brains of schizophrenics. The present study revealed that in rats lowered DBH activity was a sensitive index of noradrenergic degeneration. In the postmortem brains of 12 controls and 12 schizophrenics, however, no significant difference in DBH activity between controls and schizophrenics was found. DBH activity was relatively unstable postmortem and adversely affected by neuroleptic drugs, and these factors may have contributed to the previous finding of lowered DBH activity in the brains of schizophrenics. The activity of catechol-O-methyl transferase, which has also been previously reported as low in the brains of schizophrenics, was found to be no different in the controls of the present study.

Animals↗
PubMed1978

The locus coeruleus noradrenergic system--evidence against a role in attention, habituation, anxiety and motor activity.

Lesions of the locus coeruleus system were induced by combined stereotaxic injections of 6-OH-dopamine to the ascending fibres and just lateral to the locus coeruleus itself, to deplete the noradrenaline content of both the cerebral and cerebellar cortices. A group of rats with cortical noradrenaline concentrations of less than 30 ng/g were compared with a group with lesser destruction of the system (mean noradrenaline concentration 71 +/- 44 ng/g) and with controls (mean noradrenaline 347 +/- 58 ng/g). Lesioned rats showed normal motor activity and exploration (assessed with a holeboard) and showed normal habituation of these behaviours. The lesioned rats gave no evidence of increased susceptibility to distracting auditory stimuli whilst licking for water, and the groups did not differ in their rate of habituation to these stimuli, or in dishabituation. In a social interaction test, lesioned animals showed a decrease in social contacts in an unfamiliar situation (interpreted as a response to anxiety) of similar magnitude to that seen in the control group. In this test, lesioned animals engaged in more 'aggressive' behaviour (boxing and wrestling) than did the controls. These findings are incompatible with hypotheses that the locus coeruleus system is an integral part of the physiological mechanisms which control gross motor behaviour, attention, habituation or anxiety. Together with previous findings with the benzodiazepines, the results with the social interaction test make it unlikely that the benzodiazepines exert their anxiolytic effects by inhibiting the locus coeruleus system.

Acoustic Stimulation↗
PubMed1978

Increased dopamine-receptor sensitivity in schizophrenia.

Dopaminergic mechanisms have been investigated in post-mortem brain specimens from nineteen patients with schizophrenia and nineteen controls. Dopamine turnover was not increased in schizophrenic patients but, as assessed by the spiroperidol-binding technique, there was a significant increase in postsynaptic receptor sensitivity. The change in the dopamine receptor occurred in nucleus accumbens, putamen, and caudate nucleus. Increased dopamine-receptor sensitivity was present in five patients who had been free of neuroleptic medication for at least 1 year before death, and therefore may be related to the disease process.

Aged↗
PubMed1977

Rotational behaviour and cGMP responses following manipulation of nigral mechanisms with chlordiazepoxide. Evidence for enhancement of GABA transmission by benzodiazepines.

Unilateral stereotaxic injections of 1 microgram of the soluble benzodiazepine chlordiazepoxide hydrochloride into the predominantly GABA-containing zona reticulata of the substantia nigra of amphetamine-pretreated rats induced rotational behaviour similar to that seen following unilateral elevation of nigral GABA levels and amphetamine treatment; this effect was not seen following injections into the vicinity of the predominantly dopamine-containing zona compacta. Chlordiazepoxide-induced rotations were abolished by the GABA-antagonist picrotoxin. Both chlordiazepoxide and GABA depressed production of cyclic 3',5'-guanosine monophosphate in samples of nigral tissue in vitro as estimated by radioimmunoassay. It is concluded that chlordiazepoxide may enhance GABA transmission within the substantia nigra, by some as yet unidentified mechanism, to create asymmetric activity in GABA-modulated neurones and hence induce rotation.

Aminobutyrates↗
PubMed1977

The nucleus accumbens--possible site of antipsychotic action of neuroleptic drugs?

The hypothesis that neuroleptic drugs exert their therapeutic effects by blocking dopaminergic transmission has been investigated by examining the effects of 3 neuroleptic drugs on dopamine turnover in 2 dopaminergically innervated regions of brain--the neostriatum and nucleus accumbens. The drugs chlorpromazine, thioridazine and fluphenazine, known to be therapeutically active in the treatment of schizophrenia, but to have differing incidences of extrapyramidal side effects, were administered to rats in dose ratios approximating to those effective in man. All 3 drugs induced a similar rise in the content of the dopamine metabolite homovanillic acid (HVA) in the nucleus accumbens, whilst the changes in HVA observed in the neostriatum were in the rank order in which these drugs produce extrapyramidal side effects. While the concentrations of dopamine metabolites in the frontal cortex were too low to assess the possibility that neuroleptic drugs have actions at this level, our results are consistent with the hypothesis that these drugs exert their therapeutic effects by dopamine receptor blockade in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗