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-aminobutyric acid ([3H]GABA) was studied in vitro in rat substantia nigra (SN) and globus pallidus (GP) slices. In both structures, nicotine (10(-4) M) elicited a transient increase of [H-3]GABA release lasting no more than 2.5 min. At the peak of the effect, a 18.5% and 25% increase of [H-3]GABA was observed in GP and SN slices, respectively. At lower 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]GABA release elicited by 10(-4) M nicotine was abolished when Ca2+ concentration in the superfusion medium was lowered from 2.4 to 0.4 mM. To investigate a possible dopaminergic (DA) link in the response, we examined the sensitivity of the nicotine-induced effect to DA D-1 (SCH23390) and D-2 (sulpiride) receptor antagonists. In SN, SCH23390 (10(-6) M) abolished the 10(-4) M nicotine-induced effect. In GP, sulpiride (10(-5) M) failed to modify the response. Moreover, SCH23390 partially reversed 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 appears to be mediated by DA neurons. In GP, only a part of the nicotinic response involved a DA link. A possible direct stimulation of nicotinic receptors localized on striato-pallidal terminals is discussed.