Characterization of nicotine-induced desensitization of evoked dopamine release from rat striatal synaptosomes.

Abstract:

:Nicotine has been shown to stimulate neurotransmitter release from brain tissue by acting on presynaptic receptors. In this study, the ability of nicotine pretreatment to produce functional desensitization was investigated in rat striatal synaptosomes in which the release of [3H]dopamine was measured with an in vitro superfusion system. Pretreatment of synaptosomes with low concentrations of L-nicotine resulted in a decrease in the ability of a subsequent nicotine challenge to evoke [3H]dopamine release. The IC50 for nicotine-induced desensitization was found to be 12 nM with a maximum inhibition of > 90% at 300 nM. Nicotine pretreatment did not affect the release evoked by amphetamine, veratridine, or 15 mM K+. The onset of nicotine-induced desensitization occurred with a t1/2 of 43 s at 30 nM nicotine. The temperature dependence of onset yielded a Q10 of 1.2. Recovery from desensitization was slower (t 1/2 = 4.33 min), and both the onset and recovery appeared to follow a single first-order process. Several intermittent schedules of nicotine treatment were found to be effective at inducing and maintaining desensitization. The results of this study show that nonstimulating concentrations of nicotine can produce a complete functional desensitization of subsequent nicotine-induced neurotransmitter release.

journal_name

J Neurochem

authors

Rowell PP,Hillebrand JA

doi

10.1046/j.1471-4159.1994.63020561.x

subject

Has Abstract

pub_date

1994-08-01 00:00:00

pages

561-9

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

63

pub_type

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