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 tegmental area and projects to the ventral pallidum (VP), has been recently shown to play an important role in self-stimulation reward and cocaine reward. VP also receives a GABAergic projection from nucleus accumbens (NAS). The aim of the present study was to examine the involvement of this GABAergic projection in the modulation of VP dopamine release. Both the GABAA antagonist picrotoxin (2-200 microM) and the GABAB antagonist phaclofen (20-2,000 microM), perfused locally, dose-responsively increased VP extracellular dopamine 2-2.5-fold. Cocaine (10 microM) produced a 6.5-fold increase of VP dopamine. Neither picrotoxin (200 microM), phaclofen (2,000 microM), nor GABA (20-2,000 microM) altered the response of VP dopamine to locally applied cocaine. GBR 12909 (0.5 microM), 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 microM) was added to the perfusate. The data from the present study demonstrate that the GABAergic NAS-VP projection can modulate ventral pallidal dopamine release. However, the effect of GABA on the mesopallidal dopamine system's response to locally applied cocaine may be complicated by actions of cocaine other than dopamine uptake inhibition.
Gong
W
W
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA.
Neill
D B
DB
Justice
J B
JB
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001418:Baclofen; D003042:Cocaine; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D018756:GABA Antagonists; D010852:Picrotoxin; D010879:Piperazines; D005680:gamma-Aminobutyric Acid; C052329:phaclofen; C043425:vanoxerine