Prenatal exposure of rats to antidepressant drugs down-regulates beta-adrenoceptors and 5-HT2 receptors in cerebral cortex. Lack of correlation between 5-HT2 receptors and serotonin-mediated behaviour

Changes in the binding of beta-adrenoceptors and 5-HT2 receptors and in behaviour mediated by serotonin were studied after either acute treatment or prenatal exposure of rats to antidepressant drugs. Chlorimipramine, iprindole and mianserin reduced the density of [3H]dihydroalprenolol-labelled beta-adrenoceptors and of [3H]spiperone-labelled 5-HT2 receptors in 25-day-old rats after prenatal exposure to these drugs from gestational day 6 to delivery. Prenatal exposure to nomifensine reduced also the number of beta-adrenoceptors but, in contrast, the density of 5-HT2 receptors and the KD for binding of [3H]spiperone were markedly increased. Acute treatment of 25-day-old rats with the same antidepressants did not modify in any case the characteristics of binding to beta-adrenergic or 5-HT2 receptors. The behavioural syndrome induced by 5-hydroxytryptophan and clorgyline was only antagonized on acute treatment by mianserin. Chronic treatment in utero with the antidepressants produced varied effects on the serotonin syndrome and there was no correlation between the number of 5-HT2 receptors and the intensity of the behaviour mediated by serotonin. The observed changes in beta-adrenergic and 5-HT2 receptors after prenatal exposure to antidepressant drugs appear to be more marked and longer-lasting than those induced by chronic treatment of adult rats.