Lack of Stereoselectivity in Ability of Nicotine to Release Dopamine from Rat Synaptosomal Preparations

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Abstract
Both the naturally occurring (—)-isomer and the synthetic (+)-isomer of nicotine caused release of 3H from a crude synaptosomal fraction of rat brain prein-cubated with [3H]dopamine. The isomers were equipotent in producing this response, which was concentration-dependent, a significant effect on the fractional release of dopamine being observed at 10−4M nicotine. The effect did not appear to be the result of synaptosomal damage, as levels of the intrasynaptosomal marker lactate dehy-drogenase did not increase in the supernatant. Nicotine-induced release was inhibited by removal of external Ca2+ and by the presence in vitro of pempidine (230 μ.M). Neither hexamethonium (500 μ.M) in vitro nor the chronic administration of (-)-nicotine in vivo had any effect on the nicotine-induced release of [3H]dopamine. It is concluded that nicotine exerts this effect via a presynaptic nicotinic receptor of the “ganglionic” type, but that this receptor differs from that in the periphery by showing a relative lack of stereospecificity. There is no evidence of a functional “down regulation” in this receptor on chronic exposure to nicotine in vivo.