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Biomedical subjects

A E Theodorou

Publications and source records attributed to A E Theodorou.

16 recordsLinked to original sources
PubMed1997

Dopamine D1 and D2 receptor binding sites in brain samples from depressed suicides and controls.

Dopamine D1 and D2 receptors were measured (by saturation binding of [3H]SCH23390 and [3H]raclopride) in caudate, putamen and nucleus accumbens, obtained at post-mortem from suicide victims with a firm retrospective diagnosis of depression, and matched controls. There were no differences in the number or affinity of D1 or D2 receptors between suicides who had been free of antidepressants for at least three months prior to death, and controls. Increased numbers and decreased affinity of D2 receptors were however found in each brain region of antidepressant-treated suicides. We argue that these increases are related to concurrent treatment with neuroleptics rather than a direct effect of antidepressants. Increased numbers of D1 receptors in antidepressant-treated suicides were seen only in nucleus accumbens. This increase could not be clearly attributed to neuroleptics and may be related to antidepressant treatment.

Adolescent↗
PubMed1993

Growth hormone and physiological responses to clonidine in depression.

Clonidine (1.3 micrograms/kg) was administered to 62 control and 55 depressed patients free of psychoactive drugs for at least 7 days and fasted overnight. Growth hormone (GH), pulse, blood pressure and sedation were measured every 15 min for 1 h before and 2 h after clonidine infusion. GH response did not differ significantly between control and depressed subjects overall or when divided by sex. The systolic hypotensive and sedative responses were blunted in depressed subjects compared with controls; these effects appeared to be secondary to residual antidepressant drugs since the differences were only significant for those depressed subjects with short drug-free intervals. No differences between depressed subjects and controls were seen in diastolic hypotensive or bradycardic responses and no differences in GH, cardiovascular or sedative responses were found between endogenous and non-endogenous depressed subjects.

Adult↗
PubMed1991

Platelet alpha 2-adrenoceptors, defined with agonist and antagonist ligands, in depressed patients, prior to and following treatment.

Saturation binding of the alpha 2-adrenoceptor antagonist, 3H-yohimbine, and displacement of 3H-yohimbine with the alpha 2-adrenoceptor agonist, UK-14,304, were performed concurrently in platelet membranes obtained from drug-free depressed patients and healthy volunteers. Where possible platelet binding was repeated in depressed patients following treatment. The number and affinity of 3H-yohimbine binding sites did not differ between controls and depressed patients, or when depressed patients were divided on the basis of endogenicity (Newcastle or RDC criteria) or dexamethasone test result. The proportion of alpha 2-adrenoceptor binding sites with high affinity for UK-14,304 and KD values for the two states of the receptor did not differ in the total sample of depressed patients compared to controls. The KD for both states of the receptor and the proportion of sites with high affinity for UK-14,304 was lower in RDC non-endogenous patients than RDC endogenous patients. Treatment did not alter the total number of alpha 2-adrenoceptors or the proportion of sites with high affinity for UK-14,304, but reduced the KD for 3H-yohimbine and the KD of UK-14,304 for the low affinity state of the alpha 2-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1991

Platelet [3H]imipramine and alpha 2-adrenoceptor binding in normal subjects during desipramine administration and withdrawal.

The effect of desipramine 150 mg daily on platelet [3H]imipramine and alpha 2-adrenoceptor binding sites was studied over a 6-week period and for 6 weeks after withdrawal. Modest (10%) increases in [3H]imipramine binding site densities during treatment were noted with a decrease between 1 and 4 weeks after withdrawal. No effect was found on alpha 2-adrenoceptors. Time of day appeared to have some effect on the results found. None of the [3H]imipramine binding site effects of desipramine, on treatment or following withdrawal, was comparable in magnitude to trait differences that were also found between subjects.

Adult↗
PubMed1990

3H-imipramine binding to previously frozen platelet membranes from depressed patients, before and after treatment.

3H-imipramine binding in 39 drug-free patients with major depression and 44 healthy controls did not differ significantly between the two groups, in male or female subjects or in subgroups of depressed patients divided by endogenicity or dexamethasone suppression test result. 3H-imipramine binding in depressed patients drug-free for less than three weeks did not differ from those drug-free for longer intervals or from controls. A significant seasonal variation of 3H-imipramine Bmax was found, with lower values in summer and autumn. Treatment of depressed patients with imipramine or lofepramine for six weeks increased KD and Bmax. Methodological modification (in preparation and storage of platelets) does not explain the major differences in results between this study (using frozen platelets), a previous one (using freshly prepared platelets) and others in general, although it might contribute to the range of values reported.

Adult↗
PubMed1989

3H-imipramine binding to freshly prepared platelet membranes in depression.

3H-Imipramine binding was measured in freshly prepared platelet membranes from 47 drug-free major depressives and 46 healthy controls. Where possible, platelet binding in depressed subjects was repeated following treatment. A significant negative correlation was found between Bmax and assay protein concentration and Bmax values were corrected for this effect. Adjusted Bmax was significantly lower (by 14%) in female depressed patients than in female control subjects, and the difference was of similar magnitude premenopausally and postmenopausally. No such difference was found in males. Kd did not differ significantly between depressed and control subjects. Multiple regression analysis confirmed significant effects on Bmax of presence of depressive illness, age (positive correlation), and season (higher in summer). Within the depressed sample, Bmax was significantly lower in those subjects with obsessional features. Endogenicity (Research Diagnostic Criteria or Newcastle), dexamethasone suppression test result, drug-free interval, family history of depression, depressive psychosis, suicidal ideation, and past history of suicide attempts were not significantly related to Bmax. Paired comparisons revealed no significant effect on Bmax of 6 weeks' treatment with imipramine, maprotiline, or BRL 14342 or of a course of electroconvulsive therapy.

Adult↗
PubMed1987

Platelet alpha 2-adrenoceptor binding and function during the menstrual cycle.

Blood platelet receptors are widely used as peripheral models of central nervous system receptors, particularly in attempts to understand the biological basis of a number of neurological and psychiatric disorders. It is important to differentiate factors other than the primary disease process which may influence platelet receptors. One such potential factor is the menstrual cycle. In this study we have determined platelet high-affinity alpha 2-adrenoceptor binding, using the agonist ligand 3H-UK-14,304 and platelet aggregatory responses to adrenaline in 14 healthy young women, sampled on four occasions at weekly intervals. Our results indicate that, within the limits of individual variation, neither the KD or Bmax of high-affinity 3H-UK-14,304 binding or the aggregatory responses to adrenaline differed significantly between various stages of the menstrual cycle.

Adolescent↗
PubMed1987

Alpha 2-adrenoceptors in depression.

Studies of the mode of action of antidepressant treatments and the biological basis of depression have recently concentrated on monoamine neurotransmitter receptors. This paper reviews the studies relating to alpha 2-adrenoceptors. Chronic administration of some but not all antidepressant treatments to animals alters the number and function of brain alpha 2-adrenoceptors. In man, platelet alpha 2-adrenoceptors have been widely studied as a quantifiable peripheral model of central alpha 2-adrenoceptors. The majority of studies have not identified clear differences in platelet alpha 2-adrenoceptors between drug-free depressed patients and control subjects, nor have they identified unequivocal effects of antidepressant treatments. Methodological problems and choice of radioligand may contribute to discrepancies between studies. Central alpha 2-adrenoceptor function in man has been assessed by measuring neuroendocrine and physiological responses to clonidine. Despite considerable variation in procedure, in diagnostic criteria, and in the interval since previous treatment, most studies find the growth hormone response attenuated in depressed patients. This provides the strongest evidence to date of an abnormality of alpha 2-adrenoceptors in depression. However, it seems likely that none of the measures to date adequately mirrors the function of the cortical and limbic receptors implicated in the pathophysiology of depression. It is also likely that no single neurotransmitter abnormality is common to all depressed subjects and that future studies should be aimed at the inter-relationship and dysregulation of several neurotransmitter systems.

Animals↗
PubMed1986

Platelet high affinity adrenoceptor binding sites labelled with the agonist [3H]UK-14,304, in depressed patients and matched controls.

Increased numbers of platelet high affinity alpha 2-adrenoceptors binding sites have been reported in depressed patients using the agonist radioligand [3H]clonidine, whereas no differences from controls have been found using antagonist radioligands. We have measured platelet high affinity alpha 2-adrenoceptors in 13 depressed patients and 14 well-matched controls using a new selective agonist radioligand, [3H]UK-14,304. Unlike previous studies using [3H]clonidine, we find no differences in Bmax or KD of the high affinity alpha 2-adrenoceptor binding sites between the 2 groups.

Adult↗
PubMed1986

Platelet radioligand binding and neuroendocrine challenge tests in depression.

The purpose of this work was to examine the number and function of alpha 2-adrenoceptors and the number of serotonin uptake sites in depressed patients and controls. Platelet alpha 2-adrenoceptors and platelet serotonin uptake sites were labelled with [3H]yohimbine and [3H]imipramine respectively. Central alpha 2-adrenoceptor function was assessed by growth hormone and other responses to challenge with the alpha 2-agonist clonidine. No overall difference in the binding parameters was observed between the control and depressed groups, but the results highlight the importance of drug-free interval, menopausal status and membrane protein concentration within the binding assays in the interpretation of such studies. The growth hormone response to clonidine tended to be blunted in depressed females and was significantly blunted in the subgroup of depressives who failed to suppress plasma cortisol concentrations in response to dexamethasone. Depressed subjects also showed a smaller decrease in diastolic blood pressure and a smaller increase in sedation than control subjects.

Adult↗
PubMed1985

Platelet 3H-imipramine binding in pregnancy and the puerperium.

Platelet 3H-imipramine binding was examined in a cross-sectional study of 70 Caucasian women in pregnancy and the early post-partum period, and in 23 nonpregnant women of childbearing age. Mood was also assessed in the pregnancy and post-partum sample. No significant differences in number of binding sites (Bmax) were found, but an increase in the equilibrium dissociation constant (Kd) was demonstrated at 5-7 days post-partum.

Adult↗
PubMed1983

Cation specificity of 3H-sulpiride binding involves alteration in the number of striatal binding sites.

Specific 3H-sulpiride binding to rat striatal membranes shows an absolute requirement for the presence of sodium ions in the incubation buffer. Potassium, rubidium and caesium ions were unable to initiate specific 3H-sulpiride binding in a sodium free buffer, and lithium ions could only partially replace sodium ions. Specific 3H-spiperone binding was unaffected by variation of the cation content of the incubation buffer. The alteration in 3H-sulpiride binding caused by sodium and lithium ions was due predominantly to an increase in the number of available binding sites, rather than to altered receptor affinity. Sodium ions may be essential for the accessability of 3H-sulpiride to a single site labelled also by 3H-spiperone. However, the Ki value for sulpiride displacement of 3H-spiperone in the presence of sodium ions was 20 times greater than the KD value for 3H-sulpiride binding. So, 3H-sulpiride may interact with a highly sodium dependent binding site distinct from that labelled by 3H-spiperone.

Animals↗
PubMed1982

Increased striatal acetylcholine after 14 months cis-flupenthixol treatment in rats suggests functional supersensitivity of dopamine receptors.

Rats received continuous administration of cis-flupenthixol (0.8-1.2 mg/kg/day) or trans-flupenthixol (0.9-1.2 mg/kg/day) in drinking water for 14 months. The administration of cis-flupenthixol, but not trans-flupenthixol, caused apparent cerebral dopamine receptor supersensitivity. Thus, animals receiving cis-flupenthixol, but not trans-flupenthixol, showed enhanced apo-morphine-induced stereotyped behaviour. Dopamine concentration in striatum was not altered by drug treatment but striatal HVA and DOPAC concentrations were reduced in animals receiving cis-flupenthixol, but not trans-flupenthixol. No consistent change in Bmax of KD for specific striatal 3H-spiperone binding was observed after 14 months drug intake. However, in cis-flupenthixol treated animals a 40% increase in Bmax was observed following 2 weeks drug withdrawal. Continuous cis-flupenthixol intake increased striatal acetylcholine concentrations; trans-flupenthixol was without effect. This suggests the apparent increase in cerebral dopamine receptor supersensitivity caused by continuous long-term cis-flupenthixol administration is of functional importance in the intact animal.

Acetylcholine↗
PubMedDate not supplied

[3H]yohimbine binding to platelet alpha 2-adrenoceptors in depression.

[3H]Yohimbine binding to platelet alpha 2-adrenoceptors was studied in depressed patients and healthy volunteers. Where possible platelet binding measurement was repeated in depressed patients following treatment. Bmax of [3H]yohimbine binding did not differ significantly between depressed patients and control subjects and did not change with treatment in depressed patients. KD was significantly lower in female depressed patients, particularly in those who were post-menopausal. Multivariate analysis showed significant effects on KD of depression, season of testing and assay protein concentration.

Adult↗
PubMedDate not supplied

Alpha-1-acid glycoprotein in major depressive and eating disorders.

Plasma alpha 1-acid glycoprotein (AGP) levels were measured in 49 subjects with major depressive disorder, 15 subjects with anorexia nervosa and 18 subjects with bulimia nervosa, together with age- and sex-matched controls. AGP levels were elevated in depression and bulimia compared to controls. They were particularly elevated in depressed subjects who proved unresponsive to treatment with a standard course of antidepressants. In the depressed subjects, elevated AGP levels returned to control levels after treatment whether or not treatment was successful. There was a correlation between AGP and post-dexamethasone plasma cortisol levels in depression but not in bulimia and a correlation with age in depressed subjects only. There was no correlation between AGP values and tritiated imipramine binding parameters. Further studies are suggested to explore the issue of whether variations in AGP level are responsible for the abnormalities in platelet 5HT uptake and tritiated imipramine binding that have been reported in depression or for treatment non-response.

Anorexia Nervosa↗