Is an alpha-conotoxin MII-sensitive mechanism involved in the neurochemical, stimulatory, and rewarding effects of ethanol?
Ethanol and nicotine are the most commonly abused drugs among human beings, and a large body of evidence, from both epidemiologic and preclinical studies, indicates that there is a positive correlation between intake of both drugs. Findings of studies from our research group have demonstrated that nicotinic acetylcholine receptors, especially those located in the ventral tegmental area, are important for the stimulatory, rewarding, and dopamine-enhancing effects of ethanol. Furthermore, results of recent work indicate that the alpha4beta2* and the alpha7* receptor subunits of the nicotinic acetylcholine receptors do not seem to be involved in the neurochemical and behavioral effects of ethanol in rodents. The aim of the current study was to investigate further the role of different nicotinic acetylcholine receptor subunits in the stimulatory, dopamine-enhancing, and rewarding effects of ethanol in rodents by using the peptide alpha-conotoxin MII (5 nmol; an antagonist of the alpha3beta2*, beta3*, and alpha6* subunits of the nicotinic acetylcholine receptor) administered locally into the ventral tegmental area. A significant reduction of ethanol-induced accumbal dopamine overflow, measured by means of in vivo microdialysis, and of locomotor stimulation was observed in mice. Furthermore, alpha-conotoxin MII was demonstrated to reduce voluntary ethanol intake significantly in both rats and mice. These results indicate that alpha-conotoxin MU-sensitive receptors may be important in mediating the stimulatory, dopamine-enhancing, and rewarding effects of ethanol, and that alpha-conotoxin MII-sensitive receptors may constitute targets for development of new adjuvant for treatment of ethanol dependence.
Larsson
Anna
A
Institute of Physiology and Pharmacology, Department of Pharmacology, The Sahlgrenska Academy, Göteborg University, Box 431, SE-405 30 Göteborg, Sweden.
Jerlhag
Elisabet
E
Svensson
Lennart
L
Söderpalm
Bo
B
Engel
Jörgen A
JA
D000818:Animals; D020916:Conotoxins / Q000008:administration & dosage*; D000431:Ethanol / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D012201:Reward
D020916:Conotoxins; D011978:Receptors, Nicotinic; C098872:alpha-conotoxin MII; D000431:Ethanol