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Presynaptic Nicotinic Modulation of Dopamine Release in the Three Ascending Pathways Studied by In Vivo Microdialysis: Comparison of Naive and Chronic Nicotine‐Treated Rats
Author(s) -
Marshall David L.,
Redfern Peter H.,
Wonnacott Susan
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68041511.x
Subject(s) - nicotine , dopamine , mecamylamine , nucleus accumbens , nicotinic agonist , dopaminergic , microdialysis , chemistry , striatum , endocrinology , 3,4 dihydroxyphenylacetic acid , pharmacology , medicine , neuroscience , biology , receptor , homovanillic acid , serotonin
The modulation of dopamine release by presynaptic nicotinic receptors in vitro is well established, but the significance of this effect in vivo is unclear. We have characterised the effect of nicotine, locally applied via a microdialysis probe, on dopamine release from the terminal regions of three ascending dopaminergic pathways in conscious, freely moving rats. Nicotine caused a dose‐dependent increase in dopamine release in the striatum, the nucleus accumbens, and, to a lesser extent, the frontal cortex. Metabolite levels were unaltered by any concentration of nicotine. Prior administration of mecamylamine via the probe abolished the nicotine‐evoked increase in dopamine release, confirming the mediation of nicotinic receptors. The dose dependence of mecamylamine‐sensitive, nicotine‐evoked dopamine release was similar in all three brain regions. However, 10 −5 M tetrodotoxin totally blocked nicotine‐stimulated dopamine release in the striatum and the accumbens but not the cortex. Daily subcutaneous injections of nicotine (0.4 mg kg −1 for 7 days) increased the response to a subsequent local application of nicotine in the striatum, and a similar trend was found in the other brain areas. The same daily dose of nicotine given as a continuous infusion had no effect, whereas infusion of 4 mg kg −1 day −1 increased the response to a subsequent nicotine challenge. The localisation and regulation of nicotinic receptors in the terminal fields of dopaminergic pathways are discussed.