Prenatal exposure of rats to antidepressants enhances agonist affinity of brain dopamine receptors and dopamine-mediated behaviour

Abstract

The effects of acute treatment or prenatal exposure of rats to antidepressants on locomotor activity and [3H]spiroperidol binding to striatal membranes were studied in 25 day old rats. Prenatal exposure or acute treatment with the antidepressants chlorimipramine, iprindole or mianserin reduced locomotor activity on postnatal day 25. On the contrary, prenatal exposure to nomifensine induced locomotor hyperactivity. It was also found that chlorimipramine, iprindole or nomifensine enhanced the locomotor response to apomorphine. Acute treatment with mianserin, markedly decreased locomotion but in utero mianserin did not modify the apomorphine-induced hyperactivity. Scatchard analysis showed no change in the characteristics of binding of [3H]spiroperidol to striatal dopamine receptors after antidepressant treatment. However, the ability of dopamine to compete for these sites was significantly enhanced after prenatal exposure to all the antidepressants. This increase in agonist affinity for dopamine receptors may explain the long-lasting behavioural supersensitivity of dopamine receptors observed after chronic treatment with typical or atypical antidepressants.