IMPORTANCE OF SEROTONERGIC MECHANISMS FOR THE INDUCTION OF HYPERACTIVITY BY AMPHETAMINE AND ITS ANTAGONISM BY INTRA-ACCUMBENS (3,4-DIHYDROXY-PHENYLAMINO)-2-IMIDAZOLINE (DPI)

The present studies analyzed the role of serotonergic mechanisms in the action of two agents having purportedly different actions on the dopamine mechanisms of the rat nucleus accumbens. amphetamine and (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI). Amphetamine, given by the intraperitoneal or intra-accumbens route, caused locomotor hyperactivity. This was shown to be specific for dopamine since it was antagonized by the dopamine antagonist, fluphenazine, but not by the α- and β-adrenolytics, piperoxan and propranolol, or the cholinolytic, atropine. Intra-accumbens DPI antagonized the amphetamine hyperactivity and this effect was not mimicked by the α-agonist, clonidine. The importance of serotonin for the actions of both amphetamine and DPI was established. Thus, intra-accumbens serotonin reduced amphetamine hyperactivity whilst lesions of the medial raphé nucleus, which depleted mesolimbic serotonin, enhanced the same response. Further, the inhibitory effects of DPI against amphetamine were antagonized by the serotonergic antagonists, methysergide and cypro-heptadine, but not by piperoxan, propranolol or atropine. Also, lesions of the medial raphé nucleus markedly reduced the inhibitory effect of DPI. Finally, threshold doses of intra-accumbens DPI and serotonin synergized to reduce amphetamine hyperactivity. © 1979.