FACILITATION OF STRIATAL ACETYLCHOLINE-RELEASE BY DOPAMINE D-1 RECEPTOR STIMULATION - INVOLVEMENT OF ENHANCED NITRIC-OXIDE PRODUCTION VIA NEUROKININ-2 RECEPTOR ACTIVATION

The regulation of striatal cholinergic function by dopamine D-1 recept or activation was examined in vivo in urethane-anaesthetized rats with microdialysis probes. Extracellular acetylcholine levels were enhance d by activation of D-1 receptors either directly by a striatal applica tion of the D-1 receptor agonist (+)-SKF-38393 (3 mu M) or indirectly by the release of dopamine evoked by striatal application of neurotens in (0.1 mu M) under D-2 receptor blockade. SR 144190, a new potent and selective non-peptide neurokinin-2 receptor antagonist (0.03-1 mg/kg, i.p.), dose-dependently reduced the acetylcholine release induced by (+)-SKF-38393 or neurotensin. Furthermore, intrastriatal application o f SR 144190 (1 nM) blocked the increase in acetylcholine release induc ed by the local application of (+)-SKF-38393 (3 mu M), neurokinin A (1 mu M) or substance P (1 mu M). Finally, a role for nitric oxide in me diating the effects of D-1-neurokinin-2 receptor activation on acetylc holine release is proposed since local infusion of the competitive inh ibitor of nitric oxide synthase, N-G-monomethyl-L-arginine (0.01-10 mu M), blocked the increase in acetylcholine release induced by (+)-SKF- 38393 (3 mu M), neurotensin (0.1 mu M) or neurokinin A (1 mu M) withou t affecting the enhancing effect of the neurokinin-1 agonist septide ( 0.1 mu M). (C) 1998 IBRO. Published by Elsevier Science Ltd.