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Striatal dopamine transmission is reduced after chronic nicotine with a decrease in α6‐nicotinic receptor control in nucleus accumbens
Author(s) -
Exley Richard,
Clements Michael A.,
Hartung Henrike,
McIntosh J. Michael,
Franklin Michael,
Bermudez Isabel,
Cragg Stephanie J.
Publication year - 2013
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12298
Subject(s) - nucleus accumbens , nicotine , nicotinic agonist , dopamine , chemistry , acetylcholine receptor , endocrinology , medicine , pharmacology , nicotinic acetylcholine receptor , receptor , biochemistry
Nicotine directly regulates striatal dopamine ( DA ) neurotransmission via presynaptic nicotinic acetylcholine receptors (n AC h R s) that are α6β2 and/or α4β2 subunit‐containing, depending on region. Chronic nicotine exposure in smokers upregulates striatal n AC h R density, with some reports suggesting differential impact on α6‐ or α4‐containing n AC h R s. Here, we explored whether chronic nicotine exposure modifies striatal DA transmission, whether the effects of acute nicotine on DA release probability persist and whether there are modifications to the regulation of DA release by α6‐subunit‐containing (*) relative to non‐α6* nA C h R s in nucleus accumbens ( NA c) and in caudate‐putamen ( CP u). We detected electrically evoked DA release at carbon‐fiber microelectrodes in striatal slices from mice exposed for 4–8 weeks to nicotine (200 μg/mL in saccharin‐sweetened drinking water) or a control saccharin solution. Chronic nicotine exposure subtly reduced striatal DA release evoked by single electrical pulses, and in NA c enhanced the range of DA release evoked by different frequencies. Effects of acute nicotine (500 n m ) on DA release probability and its sensitivity to activity were apparent. However, in NA c there was downregulation of the functional dominance of α6‐n AC h R s (α6α4β2β3), and an emergence in function of non‐α6* n AC h R s. In CP u, there was no change in the control of DA release by its α6 n AC h R s (α6β2β3) relative to non‐α6. These data suggest that chronic nicotine subtly modifies the regulation of DA transmission, which, in NA c, is through downregulation of function of a susceptible population of α6α4β2β3 n AC h R s. This imbalance in function of α6:non‐α6 n AC h R s might contribute to DA dysregulation in nicotine addiction.