STIMULATION BY NICOTINE OF THE SPONTANEOUS RELEASE OF [H-3] GAMMA-AMINOBUTYRIC-ACID IN THE SUBSTANTIA-NIGRA AND IN THE GLOBUS-PALLIDUS OF THE RAT

The effect of (-)-nicotine on the spontaneous release of [H-3]gamma-am inobutyric acid ([3H]GABA) was studied in vitro in rat substantia nigr a (SN) and globus pallidus (GP) slices. In both structures, nicotine ( 10(-4) M) elicited a transient increase of [H-3]GABA release lasting n o more than 2.5 min. At the peak of the effect, a 18.5% and 25% increa se of [H-3]GABA was observed in GP and SN slices, respectively. At low er concentration (10(-5) M), nicotine produced a small but significant transient increase (+8%) in GP slices whereas this concentration was ineffective in SN slices. Pempidine (10(-5) M) totally antagonized the 10(-4) M nicotine-induced effect in SN and GP. The increase of [H-3]G ABA release elicited by 10(-4) M nicotine was abolished when Ca2+ conc entration in the superfusion medium was lowered from 2.4 to 0.4 mM. To investigate a possible dopaminergic (DA) link in the response, we exa mined the sensitivity of the nicotine-induced effect to DA D-1 (SCH233 90) and D-2 (sulpiride) receptor antagonists. In SN, SCH23390 (10(-6) M) abolished the 10(-4) M nicotine-induced effect. In GP, sulpiride (1 0(-5) M) failed to modify the response. Moreover, SCH23390 partially r eversed the nicotine-induced effect (-37%) in GP. Taken together these results indicate that nicotine differentially modulate the [H-3]GABA release in SN and GP. In SN, the nicotine-induced [H-3]GABA release ap pears to be mediated by DA neurons. In GP, only a part of the nicotini c response involved a DA link. A possible direct stimulation of nicoti nic receptors localized on striato-pallidal terminals is discussed.