Role of the parafascicular thalamic nucleus and N-methyl-D-aspartate transmission in the D1-dependent control of in vivo acetylcholine release in rat striatum.

Abstract

We investigated the involvement of glutamatergic neurotransmission in the modulation of D1 receptor-mediated stimulation of acetylcholine outflow in dorsal striatum in freely moving rats, and the relative roles of the thalamostriatal and corticostriatal pathways in this regulation using in vivo microdialysis. The selective N-methyl-D-aspartate non-competitive antagonist dizocilpine maleate (0.1 mg/kg i.p.), but not the kainate/quisqualate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (3 micrograms per side i.c.v.), completely prevented the rise in striatal extracellular acetylcholine elicited by maximal effective doses of the full D1 agonist SKF 82958 (3 mg/kg s.c.) and of the dopamine releaser d-amphetamine (2 mg/kg s.c.). Acute bilateral electrolytic lesions of the parafascicular nucleus of the thalamus prevented the stimulation of striatal acetylcholine output by SKF 82958 and d-amphetamine but only slightly reduced basal acetylcholine release. In contrast acute interruption of the corticostriatal pathway did not alter the effect of the two dopaminergic drugs although it markedly reduced basal striatal acetylcholine release. Lesions of the parafascicular thalamic nucleus, or a low dose of dizocilpine maleate (0.1 mg/kg i.p.), also prevented the acetylcholine-increasing effect of the neuroleptic remoxipride (10 mg/kg s.c.), an effect known to be D1 receptor dependent. The results suggest that striatal projections arising from the parafascicular thalamic nucleus and utilizing N-methyl-D-aspartate receptors play a critical role in the D1-mediated stimulation of acetylcholine release in dorsal striata.