Alcohol and Alcoholism Advance Access originally published online on June 23, 2006
Alcohol and Alcoholism 2006 41(5):486-493; doi:10.1093/alcalc/agl049
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ROLE OF THE SUBUNIT COMPOSITION OF CENTRAL NICOTINIC ACETYLCHOLINE RECEPTORS FOR THE STIMULATORY AND DOPAMINE-ENHANCING EFFECTS OF ETHANOL
1 Institute of Physiology and Pharmacology, Department of Pharmacology, Göteborg University, Box 431, SE 405 30 Göteborg, Sweden and 2 Department of Chemistry, Medicinal Chemistry, Göteborg University, SE 412 96 Göteborg, Sweden
* Author to whom correspondence should be addressed at: Tel.: +46 31 773 34 16; Fax: +46 31 773 32 84; E-mail: jorgen.engel{at}pharm.gu.se
(Received 22 December 2005; first review notified 20 January 2006; in revised form 12 May 2006; accepted 16 May 2006)
Aims: The stimulatory, rewarding, and dopamine (DA)-enhancing effects of ethanol may involve central nicotinic acetylcholine receptors (nAChR), especially those located in the ventral tegmental area (VTA). Identifying the subunit composition that mediates these effects of ethanol would increase the understanding of the neurochemical basis underlying the addictive properties of ethanol. In the present series of experiments, the role of the 
and/or 
and/or 
subunits of the nAChR for the stimulatory and DA-enhancing effects of ethanol was investigated by using 
-conotoxin MII (CtxMII), selective to the and/or and/or the subunits of the nAChR, and the -conotoxin PIA-analogue (CtxPIA-analogue), suggested to be selective to the subunits. Methods: CtxMII and the CtxPIA-analogue were synthesized using a modified literature procedure. The purity and identity of the peptides were confirmed with HPLC and FAB-MS analyses, respectively. Locomotor activity and in vivo microdialysis in freely moving mice were used. Results: CtxMII and the CtxPIA-analogue were synthesized in good yields (>95%; >90%). In addition, we found that synthesized CtxMII antagonized ethanol-induced locomotor stimulation, which confirms our previous results with the commercially available CtxMII. Furthermore, the synthesized CtxPIA-analogue, assumably also selective for subunits of the nAChR, did neither antagonize the stimulatory nor the accumbal DA-enhancing effects of ethanol. Conclusion: These results indicate that CtxMII- but not CtxPIA-analogue-sensitive receptors, i.e. the and/or rather than the subunits of the nAChR, appear to be of greater importance for these effects of ethanol and that these subunits could constitute neurochemical targets for developing new drugs for the treatment of alcohol dependence.
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