Inhibition of drug-induced circling by GABA-ergic activity in the nucleus accumbens.
Injections of GABA (125-500 micrograms in 1 microliter) or muscimol (40-200 ng in 1 microliter) into the nucleus accumbens markedly reduced the amphetamine-induced circling of rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of nigrostriatal dopamine neurons. The potency of muscimol was approximately 10(4) times that of GABA. Muscimol exerted a similar effect when injected in a smaller volume (0.5 microliter) at a slower rate (0.11 microliter/min), a procedure which was shown to reduce the spread of injected [3H]muscimol. Intra-accumbens injections of subconvulsive doses of picrotoxin had no effect on amphetamine-induced circling. Intra-accumbens muscimol (40 ng, 0.5 microliter, 0.11 microliter/min) also reduced the contralateral circling evoked by apomorphine in rats with unilateral 6-OHDA-induced lesions of the nigrostriatal pathway and bilateral 6-OHDA-induced lesions of the mesolimbic dopamine terminals. These results suggest that GABA-ergic activity in the nucleus accumbens exerts an inhibitory influence on drug-induced circling. At least part of this action is at a step beyond the release of dopamine from mesolimbic terminals.
D000818:Animals; D001931:Brain Mapping; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008032:Limbic System / Q000502:physiology; D008297:Male; D009118:Muscimol / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000502:physiology*; D010852:Picrotoxin / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000502:physiology*
D003913:Dextroamphetamine; D009118:Muscimol; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid