Prenatal exposure of rats to antidepressant drugs down-regulates beta-adrenoceptors and 5-HT 2 receptors in cerebral cortex : Lack of correlation between 5-HT 2 receptors and serotonin-mediated behaviour

Abstract

Changes in the binding of β-adrenoceptors and 5-HT 2 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 β-adrenoceptors and of [ 3H]spiperone-labelled 5-HT 2 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 β-adrenoceptors but, in contrast, the density of 5-HT 2 receptors and the K d 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 β-adrenergic or 5-HT 2 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-HT 2 receptors and the intensity of the behaviour mediated by serotonin. The observed changes in β-adrenergic and 5-HT 2 receptors after prenatal exposure to antidepressant drugs appear to be more marked and longer-lasting than those induced by chronic treatment of adult rats.