Potentiation of para-hydroxyamphetamine-induced head-twitch response by inhibition of monoamine oxidase type A in the brain

T Tadano, S Satoh, N Satoh, K Kisara, Y Arai, SK Kim and H Kinemuchi

Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.

After pretreatment with either clorgyline, a monoamine oxidase (MAO)-A- selective inhibitor, or pargyline, an MAO-B-selective inhibitor with less selectivity than l-deprenyl, i.c.v. administration of para- hydroxyamphetamine (p-OHA) significantly increased both the frequency and total number of head-twitches in mice. A typical MAO-B-selective inhibitor, l-deprenyl, however, did not change the total count of the p- OHA-induced head-twitch response (HTR). These effects were also found with fixed doses of the selective MAO inhibitors when p-OHA was varied. Administration of clorgyline (1 mg/kg) or pargyline (5 mg/kg) almost inhibited completely MAO-A in the mouse forebrain, and pargyline also almost inhibited completely MAO-B. l-Deprenyl, in contrast, almost inhibited completely MAO-B without affecting MAO-A activity. Systemic administration of l-5-hydroxytryptophan also induced HTR and the total number of twitches was enhanced by clorgyline, but not by pargyline or l-deprenyl. Chlorimipramine or cocaine significantly reduced p-OHA- induced HTR, suggesting an intraneuronal site of action. Together with the presence of considerable MAO-A in 5-hydroxytryptamine (5-HT) neurons of various animal species, and possible accumulation and subsequent monoamine-releasing properties of p-OHA, the present results indicate that p-OHA might induce the HTR by interaction with intraneuronally increased 5-HT. This mechanism probably results in 5-HT release onto the postsynaptic 5-HT2 receptors. Taken together, different roles of MAO-B in "the hyperactivity syndrome" and the HTR are discussed.

Volume 250, Issue 1, pp. 254-260, 07/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics