Stimulation by nicotine of the spontaneous release of [ 3H]γ-aminobutyric acid in the substantia nigra and in the globus pallidus of the rat

Abstract

The effect of (−)-nicotine on the spontaneous release of [ 3H]γ-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 [ 3H]GABA release lasting no more than 2.5 min. At the peak of the effect, a 18.5% and 25% increase of [ 3H]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 [ 3H]GABA release elicited by 10 −4 M nicotine was abolished when Ca 2+ 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 [ 3H]GABA release in SN and GP. In SN, the nicotine-induced [ 3H]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.