Stereoselective Nicotine‐Induced Release of Dopamine from Striatal Synaptosomes: Concentration Dependence and Repetitive Stimulation

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Abstract
Using a sensitive perfusion system we have studied the nicotine-induced release of [3H]dopamine ([3H]DA) from striatal synaptosomes. Nicotine-evoked release was concentration dependent with an EC50 of 3.8 .mu.M. The response to 1 .mu.M nicotine was comparable to that to 16 mM K+; 10 .mu.M veratridine evoked a larger response. All three stimuli were Ca2+ dependent but only the response to veratridine was blocked by tetrodotoxin. Repetitive stimulations by 1 .mu.M (.sbd.)-nicotine (100 .mu.l) at 30-min intervals resulted in similar levels of [3H]DA release, higher concentrations of (.sbd.)-nicotine resulted in an attenuation of the response particularly following the third stimulation. This may reflect densensitization or tachyphylaxis of the presynaptic nicotinic receptor. The action of nicotine was markedly stereoselective: a 100-fold higher concentration of (+)-nicotine was necessary to evoke the same level of response as 1 .mu.M (.sbd.)-nicotine. It is proposed that these presynaptic nicotinic receptors on striatal terminals are equivalent to high-affinity nicotine binding sites described in mammalian brain.

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