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.