Elsevier

Neuroscience Letters

Volume 189, Issue 3, 21 April 1995, Pages 171-175
Neuroscience Letters

Nanomolar concentrations of nicotine increase the release of [3H]dopamine from rat striatal synaptosomes

https://doi.org/10.1016/0304-3940(95)11471-8Get rights and content

Abstract

Nicotine stimulates the release of several neurotransmitters from brain tissue by acting on presynaptic nicotinic acetylcholine receptors (nAChR). In this study, an in vitro superfusion system was used to measure the nicotine-evoked release of [3H]dopamine (DA) from rat striatal synaptosomes. A 2-min exposure to micromolar nicotine produces a rapid increase in [3H]DA release. With continued exposure the response declines, apparently due to conversion of the nAChRs to a high-affinity desensitized conformation. In contrast, prolonged exposure to nanomolar concentrations of nicotine, while not producing an immediate response, leads to a gradual cumulative enhancement in [3H]DA release. This effect is calcium-dependent and blocked by the nicotinic antagonist, dihydro-β-erythroidine. It is suggested that the gradual DA release in response to low concentrations of nicotine occurs as a result of either open channel properties of the desensitized receptor or an equilibrium between the high-affinity desensitized and active states of the nAChRs.

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      There is evidence that nicotinic receptors composed of different subunits differ in their pharmacological properties, and also that they are differentially distributed in the brain, which makes it more complicated to develop selective ligands with desired therapeutic properties. Nicotine stimulates dopamine release in the brain, as seen in vitro with striatal, accumbal and frontal cortical slices and synaptosomes (Westfall, 1974; Giorguieff-Chesselet et al., 1979; Sakurai et al., 1982; Rapier et al., 1988; Rowell, 1995; Whiteaker et al., 1995; Teng et al., 1997) and by indirect evidence in vivo (Nose and Takemoto, 1974; Lichtensteiger et al., 1982). Acute systemically administered nicotine has been found to facilitate dopamine output in vivo in numerous microdialysis studies (Imperato et al., 1986; Di Chiara and Imperato, 1988; Damsma et al., 1989; Benwell and Balfour, 1992; Mirza et al., 1996; Nisell et al., 1996; Benwell and Balfour, 1997; Seppa and Ahtee, 2000; Seppa et al., 2000).

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