Stimulation by nicotine of the spontaneous release of [3H]gamma-aminobutyric acid in the substantia nigra and in the globus pallidus of the rat.
The effect of (-)-nicotine on the spontaneous release of [3H]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 [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 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 D1 (SCH23390) and D2 (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.
Kayadjanian
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Laboratoire de Neurochimie-Anatomie, CNRS URA 1488, Institut des Neurosciences, Université Pierre et Marie Curie, Paris, France.
Rétaux
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S
Menétrey
A
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Besson
M J
MJ
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D001552:Benzazepines; D011954:Receptors, Dopamine; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D013469:Sulpiride; D004298:Dopamine