The effect of varenicline on binge-like ethanol consumption in mice is β4 nicotinic acetylcholine receptor-independent.
Our laboratory has previously shown that the smoking-cessation agent varenicline, an agonist/partial agonist of α4β2*, α3β4*, α3β2*, α6β2* (* indicates the possibility of additional subunits) and α7 subunits of nicotinic acetylcholine receptors (nAChRs), reduces ethanol consumption in rats only after long-term exposure (12 weeks). As compounds having partial agonistic activity on α3β4* nAChRs were shown to decrease ethanol consumption in rodents, we assessed here the involvement of the β4 subunit in the effect of varenicline in the reduction of short- and long-term binge-like ethanol drinking in mice.



We used the well-validated drinking-in-the-dark (DID) paradigm to model chronic binge-like ethanol drinking in β4-/-and β4+/+littermate mice and compare the effect of intraperitoneal injection of varenicline (2mg/kg) on ethanol intake following short- (4 weeks) or long-term (12 weeks) exposure.



Drinking pattern and amounts of ethanol intake were similar in β4-/-and β4+/+mice. Interestingly, our results showed that varenicline reduces ethanol consumption following short- and long-term ethanol exposure in the DID. Although the effect of varenicline on the reduction of ethanol consumption was slightly more pronounced in β4-/-mice than their β4+/+littermates no significant differences were observed between genotypes.



In mice, varenicline reduces binge-like ethanol consumption both after short- and long-term exposure in the DID and this effect is independent of β4 nAChR subunit.
Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Australia.
Omkar L
OL
Patkar
Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Australia.
Arnauld
A
Belmer
Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Australia.
Josephine R
JR
Tarren
Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Australia.
Joan Y
JY
Holgate
Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Australia. Electronic address: selena.bartlett@qut.edu.au.
Selena E
SE
Bartlett
D000818:Animals; D063425:Binge Drinking / Q000378:metabolism / Q000628:therapy*; D000431:Ethanol / Q000097:blood; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000068580:Varenicline / Q000627:therapeutic use*
C486720:Chrnb4 protein, mouse; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D000431:Ethanol; D000068580:Varenicline