ROLE OF DOPAMINE IN BEHAVIORAL-EFFECTS OF SEROTONIN MICROINJECTED INTO RAT STRIATUM

Bilateral local microinfusion of serotonin (5-hydroxytryptamine; 5-HT) into the ventrolateral striatum (VLS) of the rat forebrain induces qu antifiable stereotyped orofacial behaviors. The role of presynaptic do pamine (DA) and structural requirements of indoles for expression of t his behavioral effect and for inhibition of neuronal transport of [H-3 ]DA were examined. Bilateral local injection of 6-OHDA (8 mu g/side) i nto VLS depleted DA and markedly diminished the behavioral effects of 5-HT. Intracerebral pretreatment with the potent DA transport inhibito rs GBR-12909 (6 mu g/side) or nomifensine (4 mu g/side) also markedly decreased behavioral responses to 5-HT. A series of indoles and tyrami ne were examined for ability to induce stereotypy following infusion i nto the VLS. Of compounds tested, only p-tyramine, 5-HT, tryptamine an d L-5-hydroxytryptophan (5-HTP) elicited strong orofacial behaviors; i ndoles lacking a free amino group or containing other substituents wer e virtually inactive in vivo, and the effect of 5-HTP was prevented by systemic pretreatment with the decarboxylase inhibitor NSD-1015, indi cating its required conversion to 5-HT. Uptake of [H-3]DA (0.1 mu M) i nto rat striatal synaptosomes was inhibited in a concentration-depende nt manner in the following apparent rank-order: p-tyramine, N-methyl-5 -HT, tryptamine, 5-HT, N-methyltryptamine (IC50 = 44-718 nM), other in doles (IC50 = 10-100 mu M). These results support the conclusion that oral stereotypy induced by microinjection of 5-HT or other aromatic am ines into rat VLS is mediated by local release of endogenous DA. These results extend previous findings indicating that this effect of 5-HT was not blocked by 5-HT receptor antagonists, and suggest mediation by a neuronal transport process involved in the uptake or storage of DA. Copyright (C) 1997 Elsevier Science Inc.