Cocaine releases limbic acetylcholine through endogenous dopamine action on D1 receptors.
Cocaine (10 and 20 mg/kg i.p.) enhanced the extracellular concentration of acetylcholine (ACh) in the ventral striatum of freely moving rats. The enhancement was prevented both by dopamine (DA) D1 receptor blockade with SCH 23390 (0.1 mg/kg s.c.) and by depletion of endogenous DA after coadministration of reserpine (5 mg/kg i.p.) and alpha-methyltyrosine (alpha-MT) (150 mg/kg i.p.). In contrast, blockade of DA D2 receptors with (-)-sulpiride (20 mg/kg i.p.) did not prevent the cocaine-induced increase in ACh release. These results indicate that the cocaine-induced stimulation of ACh release is mediated by an action of DA on D1 receptors, and suggest that the enhancement of ACh release might play a functional role in the central effects of cocaine. Moreover, DA depletion after reserpine + alpha-MT or D1 receptor blockade with SCH 23390 led to a comparable decrease of baseline ACh release, suggesting that striatal cholinergic interneurons are under D1 receptor-mediated facilitatory dopaminergic control.
Department of Neuroscience Bernard B. Brodie, University of Cagliari, Italy.
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A
Imperato
M C
MC
Obinu
M V
MV
Demontis
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GL
Gessa
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002421:Caudate Nucleus / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D065127:Dopamine D2 Receptor Antagonists; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors; D019805:alpha-Methyltyrosine
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D008781:Methyltyrosines; D017447:Receptors, Dopamine D1; D019805:alpha-Methyltyrosine; D013469:Sulpiride; D012110:Reserpine; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine; D000109:Acetylcholine; D004298:Dopamine