GABAERGIC MODULATION OF VENTRAL PALLIDAL DOPAMINE RELEASE STUDIED BY IN-VIVO MICRODIALYSIS IN THE FREELY MOVING RAT

The mesopallidal dopamine system, which originates from the ventral te gmental area and projects to the ventral pallidum (VP), has been recen tly shown to play an important role in self-stimulation reward and coc aine reward. VP also receives a GABAergic projection from nucleus accu mbens (NAS). The aim of the present study was to examine the involveme nt of this GABAergic projection in the modulation of VP dopamine relea se. Both the GABA(A) antagonist picrotoxin (2-200 mu M) and the GABA(B ) antagonist phaclofen (20-2,000 mu M), perfused locally, dose-respons ively increased VP extracellular dopamine 2-2.5-fold. Cocaine (10 mu M ) produced a 6.5-fold increase of VP dopamine. Neither picrotoxin (200 mu M), phaclofen (2,200 mu M), nor GABA (20-2,000 mu M) altered the r esponse of VP dopamine to locally applied cocaine. GBR 12909 (0.5 mu M ), a selective dopamine uptake blocker, induced a 3.5-fold increase of VP dopamine. The increase of VP dopamine in response to GBR 12909 was further augmented to 8.5-fold of baseline when picrotoxin (200 mu M) was added to the perfusate. The data from the present study demonstrat e that the GABAergic NAS-VP projection can modulate ventral pallidal d opamine release. However, the effect of GABA on the mesopallidal dopam ine system's response to locally applied cocaine may be complicated by actions of cocaine other than dopamine uptake inhibition. Synapse 29: 406-412, 1998. (C) 1998 Wiley-Liss, Inc.