Mecamylamine decreases accumbal dopamine output in mice treated chronically with nicotine.
The role of nicotinic acetylcholine receptor (nAChR) activation in accumbal dopamine (DA) release during chronic continuous nicotine treatment was studied by in vivo microdialysis in freely-moving mice. Nicotine was administered chronically to NMRI mice in their drinking water. On the 50th day of nicotine administration microdialysis samples were collected at 20 min intervals and their DA, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid contents were measured using a high-performance liquid chromatographic-electrochemical procedure. After collection of four baseline samples the nicotinic antagonist mecamylamine (2 mg/kg, s.c.) was given. The steady-state DA output was larger in the nicotine-treated mice than in the control mice. Mecamylamine reduced the DA output in the nicotine-treated but not in the control mice. Thus, after continuous 50-day administration nicotine still continues to activate nAChRs regulating accumbal DA release.
Gäddnäs
Helena
H
Division of Pharmacology and Toxicology, Department of Pharmacy, PO Box 56, University of Helsinki, Helsinki, FIN-00014, Finland.
Piepponen
T Petteri
TP
Ahtee
Liisa
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D051379:Mice; D017551:Microdialysis; D009538:Nicotine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D008464:Mecamylamine; D009538:Nicotine; D004298:Dopamine; D006719:Homovanillic Acid