In vivo or in vitro exposure to imipramine reduces α2-adrenoceptor-mediated inhibition of cyclic AMP production in rat brain cerebral cortical slices

Abstract

The effect of in vivo or in vitro exposure to imipramine on alpha 2-adrenoceptor-mediated inhibition of cAMP production in rat brain slices was examined. Chronic administration (10 mg/kg once daily for 14 or 21 days) of imipramine or in vitro exposure (100 microM, 60 min) to the antidepressant significantly reduced the ability of UK-14,304, an alpha 2-adrenoceptor agonist, to inhibit forskolin-stimulated cAMP accumulation in cerebral cortical slices. This reduction was due to a decrease in the maximal response to the alpha 2-adrenergic agonist rather than to a decrease in its potency. Besides yielding a rapid and direct method for studying the effect of imipramine on brain receptors in vitro, these findings provide biochemical evidence in support of the notion that this drug, and perhaps other antidepressants, modifies alpha 2-adrenoceptor function in the central nervous system.