Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment.
Most antidepressant therapies require an initial period of sustained use before therapeutic effects are observed; the literature suggests that this may be due to alterations in either serotonergic or noradrenergic systems. To further explore the mechanism of action of antidepressants, the effect of 21-day drug treatment to rats on serotonin type 2 and beta-adrenergic receptors in fronto-parietal hemicortices was evaluated. Because the same brain was used to measure concomitant changes in both receptors, confounding effects due to inter-animal variability are reduced. The effect of a classical antidepressant drug, desmethylimipramine, was compared with two compounds which have more recently been used to treat depression, ie., adinazolam, a tirazolobenzodiazepine, and buspirone, a serotonin type 1A partial agonist, both of which possesses combined anxiolytic and antidepressant effects. The anxiolytic drug diazepam, a benzodiazepine devoid of antidepressant properties, was used as an active control treatment. Membrane binding studies showed that the maximal binding of [125I]cyanopindolol to beta-adrenoceptors was significantly decreased only by desmethylimipramine treatment. On the other hand, adinazolam and buspirone, as well as desmethylimipramine, decreased the maximal binding of [125I]7-amino-8-iodo-ketanserin binding to serotonin type 2 receptors. Diazepam was without effect on either receptor. These results suggest that down-regulation of serotonin type 2 receptors may be a common element in the mechanism of action of antidepressant therapies.
Lafaille
F
F
Douglas Hospital Research Centre, McGill University, Department of Psychiatry, Montreal, Quebec, Canada.
Welner
S A
SA
Suranyi-Cadotte
B E
BE
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*
D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin