Apomorphine decreases extracellular GABA in the ventral pallidum of rats with 6-OHDA lesions in the nucleus accumbens.
Inhibition of a tonically active gamma-aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is thought to mediate the locomotor response elicited by dopamine in the nucleus accumbens. To evaluate this hypothesis, dopamine was depleted in the nucleus accumbens using 6-hydroxydopamine which produced an upregulated locomotor response to systemic apomorphine (0.2 mg/kg, s.c.). Simultaneously, the level of extracellular GABA in the VP was monitored using microdialysis. Apomorphine injection produced an elevation in locomotor activity only in the lesioned rats. While apomorphine reduced extracellular GABA in both control and lesioned rats, the reduction had an earlier onset and was more consistent in lesioned animals. Although the onset of the decline in extracellular GABA in the VP of lesioned rats corresponded to the onset of apomorphine-induced motor activity, a significant reduction in GABA persisted for 180 min, while the behavior returned to control levels by 60 min after injection. These data support a possible role for dopamine receptor-mediated inhibition of accumbal GABA neurons projecting to the VP in the initiation of locomotor activity.
Bourdelais
A
A
Alcohol and Drug Abuse Program, Washington State University, Pullman 99164-6520.
Kalivas
P W
PW
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine