Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum.
Dopamine is vital for coordinated motion and for association learning linked to behavioral reinforcement. Here we show that the precise overlap of striatal dopaminergic and cholinergic fibers underlies potent control of dopamine release by ongoing nicotinic receptor activity. In mouse striatal slices, nicotinic antagonists or depletion of endogenous acetylcholine decreased evoked dopamine release by 90%. Nicotine at the concentration experienced by smokers also regulated dopamine release. In mutant mice lacking the beta2 nicotinic subunit, evoked dopamine release was dramatically suppressed, and those mice did not show cholinergic regulation of dopamine release. The results offer new perspectives when considering nicotine addiction and the high prevalence of smoking in schizophrenics.
Zhou
F M
FM
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
Liang
Y
Y
Dani
J A
JA
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D012907:Smoking / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D009467:Neuromuscular Depolarizing Agents; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013779:Tetrodotoxin; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D000109:Acetylcholine; D002118:Calcium; D004298:Dopamine