Regulation of Dopamine Release by Striatal Acetylcholine and Nicotine Is via Distinct Nicotinic Acetylcholine Receptors in Dorsal vs. Ventral Striatum
Striatal dopamine (DA) neurotransmission plays a fundamental role in the reinforcing and ultimately addictive effects of nicotine. Both nicotine and endogenous acetylcholine (ACh) regulate striatal DA release via β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) on striatal axons. The subfamily of β2*-nAChRs responsible for these potent synaptic effects could offer a molecular target for therapeutic strategies in nicotine addiction. We explored the role of the α6β2*-nAChRs in the nucleus accumbens (NAc) and caudate-putamen (CPu) by observing action potential-dependent DA release from synapses in real time using fast-scan cyclic voltammetry at carbon-fibre microelectrodes in mouse striatal slices. We show that α6β2*-nAChRs dominate in the control of DA release by ACh and nicotine in NAc but have a more minor role in CPu alongside other β2*-nAChRs (e.g. α4*). These data offer new insights to suggest striatal α6*-nAChRs as a molecular target for a therapeutic strategy for nicotine addiction.
KeywordsSingle Pulse Nicotinic Acetylcholine Receptor Dorsal Striatum Nicotine Addiction Release Probability
The authors acknowledge support from the Parkinson’s Disease Society (UK), MJ Fox Foundation, the Biotechnology and Biological Sciences Research Council (UK), and Eli Lilly UK, the Paton Fellowship (University of Oxford).
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