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Biomedical subjects

J F Deakin

Publications and source records attributed to J F Deakin.

At least 73 records · Page 4Linked to original sources
PubMed1988

5HT2 receptors, depression and anxiety.

The distinction between non-psychotic repressive illness and anxiety states is blurred. Large scale trials in the neuroses indicate that benzodiazepines are ineffective in depression, and transiently and partially effective in anxiety. In contrast, tricyclic antidepressants are effective in both. All effective antidepressants decrease 5HT2 receptors number and this may mediate antidepressant efficacy. Our studies indicate that reduction of 5HT2 relative to 5HT1 neurotransmission would reverse the neuroendocrine abnormalities we have described in depression. Reduced 5HT2 neurotransmission may also be a mechanism of anxiolytic action in view of 5HT theories of punishment. There is clinical evidence for anxiolytic and antidepressant action of selective 5HT2 antagonists.

Anxiety↗
PubMed1987

Sodium dependent D-[3H]aspartate binding in cerebral cortex in patients with Alzheimer's and Parkinson's diseases.

The sodium dependent binding of D-[3H]aspartate to the high-affinity glutamate uptake system was used as a marker of glutamate-releasing terminals in the cerebral cortex of brains from patients with Alzheimer-type dementia (ATD) and Parkinson's disease (PD). Sodium-dependent D-[3H]aspartate binding was reduced in the ATD patients but not in the PD patients. Within the PD patients no association was observed between sodium-dependent D-[3H]aspartate binding and the presence of dementia. In contrast choline acetyltransferase activity was reduced in both the ATD and the PD patients. The present results suggest that changes in the cortical cholinergic system can occur independently of the cortical glutamate system. The glutamatergic deficit in ATD may contribute to some of the clinical differences between the dementia of ATD and PD.

Aged↗
PubMed1987

A comparison of some retrograde and anterograde effects of electroconvulsive shock in patients with severe depression.

Seventy severely depressed patients were randomly assigned to receive either a standard course of bilateral electroconvulsive therapy (ECT) or a course of simulated ECT (muscle relaxant and anaesthesia) identical to the real course except that the shock was omitted. Anterograde amnesia due to the shock was demonstrated in recognition memory for word lists and in recall of labels for faces, but this was eliminated by priming. Retrograde amnesia was also present for labels for faces learned the day before a treatment, but this was not eliminated by priming. Recognition memory for material learned in the remote past was better in the patients who had received shock than in those who had received only anaesthetic.

Adult↗
PubMed1985

Cortical serotonin receptor subtypes after lesion of ascending cholinergic neurones in rat.

Serotonin (5-HT) S1 and S2 receptors were studied in rat cortex after lesion of the ascending cholinergic systems by injection of ibotenic acid into the nucleus basalis. The lesions produced a large (56%) decrease in choline acetyltransferase activity with no change in markers of gamma-aminobutyric acid, dopamine and 5-HT containing neurones. Lesions of the ascending cholinergic neurones were accompanied by a loss of 5-HT S1 receptor binding sites with no change in S2 receptors. These results suggest that a proportion of S1 receptors may be associated with cholinergic terminals.

Animals↗
PubMed1985

MHPG excretion in endogenous depression: relationship to clinical state and the effects of ECT.

In a group of 70 patients with endogenous depression entering a controlled trial of real versus sham ECT, urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) excretion was significantly reduced by comparison with previously studied groups of control subjects, of acute and chronic schizophrenic patients and of anxious patients. However, urinary MHPG was unrelated to severity of depression, or to the presence of delusions, retardation or agitation. MHPG excretion did not predict clinical outcome, or the response to ECT. Urinary MHPG content at trial entry was unrelated to past tricyclic antidepressant or benzodiazepine medication, although an influence of the latter on the findings cannot be excluded, since all patients received benzodiazepine (nitrazepam) night sedation during the trial. During the 4-week trial MHPG excretion remained low and did not increase in relation to change in clinical state, although there was a small but significant increase in patients who received real ECT. The findings confirm that urinary MHPG excretion is reduced in depression, but establish that such reductions are not state dependent. Since the increase in MHPG excretion with ECT is not related to changes in clinical state, the former presumably does not reflect the mechanism of action of ECT.

Adult↗
PubMed1985

Intertectal neuronal plasticity in Xenopus laevis: persistence despite catecholamine depletion.

In normal Xenopus, the tectum receives a direct projection from the contralateral retina and an indirect projection, via the intertectal system, from the ipsilateral eye. The two maps of binocular visual space, at each tectum, are in register. If one eye is rotated during larval development, the ipsilateral visuotectal projection compensates by changing its orientation. Rearrangement of the intertectal system brings the ipsilateral map back into register with the contralateral map. We sought to determine whether this intertectal plasticity required normal levels of brain monoamines. Animals received an eye rotation between stages 55-63 of larval life and were then placed in one of 3 groups. A first control group received no further treatment. A second control group was given intraventricular injections of ascorbate vehicle. The experimental group was given intraventricular injections of 6-hydroxydopamine in ascorbate vehicle. Two to 3 months after metamorphosis, visuotectal projections were mapped electrophysiologically and the brains were assayed for monoamines. Intertectal plasticity occurred in all 3 groups of animals, including animals in which brain catecholamine levels were severely reduced. We conclude that normal levels of brain catecholamines are not required for this form of neural plasticity.

Animals↗
PubMed1984

Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides.

In patients with Alzheimer-type dementia, in addition to the well-known losses of cholinergic neurones, there is evidence of degeneration of the noradrenergic and serotonergic innervation of the cerebral cortex. While noradrenergic and cholinergic receptors are preserved there is a loss of serotonin S1 and S2 receptors, particularly in the temporal lobe. The loss of serotonin S2 receptors may occur at an early stage of the disease and, in temporal and frontal cortex, is correlated with the loss of somatostatin immunoreactivity. In patients dying in hospital with depression, and in individuals committing suicide, there are no consistent changes in monoamine metabolites. Noradrenergic, serotonergic, and other neurotransmitter receptors were found to be unchanged, although there was a moderate decrease in imipramine binding in a small group (n = 6) of subjects with a history of depression, who had committed suicide.

Aged↗
PubMed1984

Relationships between hyponeophagia, diazepam sensitivity and benzodiazepine receptor binding in eighteen rat genotypes.

Rats of 18 genotypes derived from the selected Roman strains were tested for hyponeophagia in a control condition and following diazepam (1 mg/kg). Subsequently, benzodiazepine receptor binding was measured in the cortical/striatal region. Hyponeophagia in the control condition correlated strongly with diazepam sensitivity, but benzodiazepine receptor titres did not correlate significantly with either control behavior or drug responsivity. These findings are discussed in the contexts of the arousal hypothesis of hyponeophagia and of postulated relationships between benzodiazepine receptors and emotionality.

Animals↗
PubMed1983

The effects of cholecystokinin on dopaminergic mechanisms in rat striatum.

Intraventricular administration of cholecystokinin-octapeptide in unanesthetized rats results in a significant reduction in the number of [3H]spiperone binding sites. Striatal levels of the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were significantly reduced, whereas there was no significant reduction in the levels of the serotonin metabolite 5-hydroxyindoleacetic acid.

Animals↗
PubMed1983

[3H]etorphine binding in rat striatum following lesions of the raphe nuclei.

Following 5,7-dihydroxytryptamine lesions of the rat raphe nuclei a significant reduction in striatal serotonin concentrations was observed. However, with [3H]etorphine as ligand no change in opiate receptor binding was observed in striatal membranes. Moreover, when [3H]etorphine binding was resolved into its mu- and delta + kappa-components no change in either component was observed compared with controls. It is concluded that opiate receptors are not on striatal serotonergic nerve terminals whose cell bodies are located in the raphe nuclei.

5,7-Dihydroxytryptamine↗
PubMed1983

Studies on the mechanisms by which clenbuterol, a beta-adrenoceptor agonist, enhances 5-HT-mediated behaviour and increases metabolism of 5-HT in the brain of the rat.

The head twitch response in mice produced by injection of 5-hydroxytryptophan (100 mg/kg i.p.) and carbidopa (25 mg/kg i.p.) was enhanced by administration of clenbuterol (0.5 mg/kg i.p.), a beta-adrenoceptor agonist. Clenbuterol also enhanced the hyperactivity syndrome in rats produced by quipazine (25 mg/kg i.p.), a 5-hydroxytryptamine (5-HT) agonist. This enhancement was not prevented by depletion of 5-HT in brain with p-chlorophenylalanine or after pretreatment with prazosin. The behavioural responses of the rats to administration of the alpha 2-adrenoceptor agonist, clonidine, was unaltered by acute or longer-term administration of clenbuterol. Following chronic administration of clenbuterol (5 mg/kg daily for 14 days), a procedure resulting in down-regulation of central beta-adrenoceptors, a larger dose of clenbuterol was necessary to enhance the quipazine-induced hyperactivity, suggesting that the mechanism of enhancement involved central post-synaptic beta-adrenoceptors. Further evidence for this conclusion was that a lesion of central noradrenaline pathways produced by 6-hydroxydopamine did not abolish the clenbuterol-induced enhancement of the quipazine-mediated behaviour. The binding characteristics of 5-HT2-receptors were unchanged by acute or chronic administration of clenbuterol. Clenbuterol (5 mg/kg) increased the percentage of plasma free (non-albumin bound) tryptophan, plasma free fatty acid concentration and the concentration of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA) in the brain. The increase in 5-HT turnover in brain was prevented by pretreatment with the beta 1-adrenoceptor antagonist atenolol, which enters the brain poorly. It is therefore suggested that the clenbuterol-induced increase in 5-HT metabolism results from the increase in the concentration of plasma free fatty acid which increases plasma free tryptophan and thus increases the concentration of tryptophan in brain and 5-HT synthesis in brain. The clenbuterol-induced enhancement of 5-HT-mediated behaviour is therefore not associated with its effect on 5-HT metabolism. The data are discussed in relation to that obtained after administration of antidepressant drugs.

Animals↗
PubMed1983

Effects of ECT and depression on various aspects of memory.

Seventy severely depressed patients randomly assigned to receive 8 real or sham ECT were further subdivided on the basis of degree of recovery from depression afterwards. In comparison to a non-depressed control group the depressed patients were impaired on a wide range of tests of memory and concentration prior to treatment, but afterwards performance on most of the tests had improved. Real ECT induced impairments of concentration, short-term memory and learning, but significantly facilitated access to remote memories. At 6 months follow-up all differences between real and sham ECT groups had disappeared. On the majority of tests the previously depressed patients now performed at the same level as the control group. There was some evidence that a subgroup of treatment-resistant patients (poor outcome after real ECT) were significantly more likely to complain of memory problems 6 months later.

Adult↗
PubMed1983

Effects of ECT on pituitary hormone release: relationship to seizure, clinical variables and outcome.

Prolactin, cortisol, growth hormone and TSH serum levels (before and 15 minutes after treatment) were measured in 62 patients with endogenous depression randomly allocated to real or pseudo-ECT. Prolactin increased significantly more in those receiving real ECT than in those receiving pseudo-ECT, but the size of this effect had diminished by the time of the last (8th) treatment in the trial. Cortisol secretion was also significantly increased following the first treatment by real ECT, but this increase was of significantly smaller size in patients with delusions. Tolerance to the effects of ECT on cortisol secretion was not observed. No effects of ECT on growth hormone or TSH secretion were detected, and no clear evidence was obtained that endocrine responses can be used as a predictor of response to ECT.

Depressive Disorder↗