In vivo neurochemical evidence that stimulation of accumbal GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.

Abstract

Cholinergic neurons in the nucleus accumbens contain GABAA and GABAB receptors that are thought to inhibit neural activity. We analyzed the roles of GABAA and GABAB 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 30-60min infusions. To monitor basal acetylcholine, a low concentration of physostigmine (50nM) was added to the perfusate. GABAA receptor agonist muscimol (3 and 30pmol) induced a dose-related decrease in accumbal acetylcholine. GABAB receptor agonist baclofen (30 and 300pmol) also produced a dose-related decrease in acetylcholine. GABAA receptor antagonist bicuculline (60pmol) which failed to alter baseline acetylcholine counteracted the muscimol (30pmol)-induced decrease in acetylcholine. GABAB receptor antagonist 2-hydroxysaclofen (12nmol) which failed to change baseline acetylcholine, counteracted the baclofen (300pmol)-induced decrease in acetylcholine. Neither muscimol (30pmol) nor baclofen (300pmol) which reduced accumbal acetylcholine altered baseline accumbal dopamine. Neither bicuculline (60pmol) nor 2-hydroxysaclofen (12nmol) also affected the baseline dopamine. These results show that GABAA and GABAB 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 GABAA and GABAB receptors each reduce acetylcholine efflux without affecting dopamine efflux in the nucleus accumbens of freely moving rats.