Involvement of intrinsic cholinergic and GABAergic innervation in the effect of NMDA on striatal dopamine efflux and metabolism as assessed by microdialysis studies in freely moving rats

Microdialysis perfusion was used to study the participation of striatal cho linergic and gamma -aminobutyric acid-ergic (GABAergic) neurotransmission i n basal and N-methyl-D-aspartate (NMDA) receptor-modulated dopamine release and metabolism in the striatum of the freely moving rat. Reverse dialysis of atropine (1-50 muM) induced a concentration-related increase in dopamine efflux and decrease in 3,4-dihydroxyphenylacetic acid (DOPAC) and homovani llic acid (HVA) efflux. (+)-Bicuculline (10-100 muM) similarly increased do pamine efflux, but was without consistent effect on metabolite efflux. Reve rse dialysis of NMDA (1 mM) evoked an approximately twofold increase in dop amine efflux and decreased DOPAC and HVA efflux to 30-40% of basal levels. The effect of NMDA on dopamine efflux was completely abolished by coadminis tration of tetrodotoxin (TTX; 1 mum) or atropine (10 mum), and markedly pot entiated (approximately fourfold) by coadministration of (+)-bicuculline (5 0 mum). The NMDA-induced decrease in dopamine metabolite efflux was inhibit ed by coadministration of TTX or (+)-bicuculline, but was unaffected by atr opine. Our data suggest that dopamine release in the striatum is subject to both cholinergic and GABAergic tonic inhibitory mechanisms mediated throug h muscarinic and GABA(A) receptors, respectively. Furthermore, NMDA-stimula ted dopamine release also involves obligatory cholinergic facilitation and an inhibitory GABAergic component mediated through these respective recepto rs.