In vivo neurochemical evidence that stimulation of accumbal GABA(A) and GABA(B) receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats

摘要

Cholinergic neurons in the nucleus accumbens contain GABA(A) and GABA(B) receptors that are thought to inhibit neural activity. We analyzed the roles of GABA(A) and GABA(B) receptors in regulating accumbal acetylcholine efflux of freely moving rats using in vivo microdialysis. The effects of GABA receptor ligands on the accumbal dopamine efflux were also analyzed because accumbal cholinergic and dopaminergic neurons could mutually interact. Drugs were applied intracerebrally through the dialysis probe. Doses of compounds indicate total amount administered (mol) during 30-60 min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50 nM) was added to the perfusate. GABA(A) receptor agonist muscimol (3 and 30 pmol) induced a dose-related decrease in accumbal acetylcholine. GABA(B) receptor agonist baclofen (30 and 300 pmol) also produced a dose-related decrease in acetylcholine. GABA(A) receptor antagonist bicuculline (60 pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30 pmol)-induced decrease in acetylcholine. GABA(B) receptor antagonist 2-hydroxysaclofen (12 nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300 pmol)-induced decrease in acetylcholine. Neither muscimol (30 pmol) nor baclofen (300 pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60 pmol) nor 2-hydroxysaclofen (12 nmol) also affected the baseline dopamine. These results show that GABA(A) and GABA(B) receptors each exert inhibitory roles in the regulation of accumbal cholinergic neural activity. The present results also provides in vivo neurochemical evidence that stimulation of GABA(A) and GABA(B) receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.