Modulation of dopamine-mediated behavioural responses by antidepressants: effects of single and repeated treatment

The study concerned the effects of maprotiline, imipramine, clomipramine and amitriptyline on the stereotyped and turning behaviour induced by apomorphine in rats. At either single or repeated doses of 25 mg/kg i.p. neither maprotiline nor imipramine changed the stereotyped responses induced by apomorphine. Clomipramine showed in contrast an inhibitory effect which increased after 7 daily injections of the drug. Moderate suppression of stereotypies was also observed after repeated administration of amitriptyline. In rats with unilateral 6-OHDA lesions of the s.nigra apomorphine-induced contralateral turning was markedly suppressed (70%) after a single 25 mg/kg i.p. injection of maprotiline. A tolerance to this effect developed after 7 daily injections of the drug. Clomipramine and amitriptyline caused an inhibition of turning which was markedly increased after repeated treatment. These results suggest that antidepressants do not uniformly affect the behavioural responses mediated by dopamine. Clomipramine and amitriptyline appear to possess dopamine receptor blocking properties which may become more pronounced after chronic treatment. In contrast, the dopamine receptor blockade by maprotiline diminished and disappeared under such conditions. Among the drugs investigated imipramine was the one which seemed to have the weakest influence on dopaminergic receptors.