Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking Export

@article{citeulike:1465715, abstract = {Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence.}, address = {selenab@gallo.ucsf.edu}, author = {Steensland, P. and Simms, J. A. and Holgate, J. and Richards, J. K. and Bartlett, S. E.}, citeulike-article-id = {1465715}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0705368104}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17626178}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17626178}, day = {11}, doi = {10.1073/pnas.0705368104}, journal = {Proceedings of the National Academy of Sciences of the USA}, keywords = {acetylcholine, alcohol, animals, champix, nicotine, pharmacotherapy, varenicline}, month = {July}, number = {30}, pages = {12518--12523}, posted-at = {2007-07-18 22:17:54}, priority = {3}, title = {Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking}, url = {http://dx.doi.org/10.1073/pnas.0705368104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:1465715 L3 - citeulike-article-id:1465715 N2 - Alcohol dependence is a disease that impacts millions of individuals worldwide. There has been some progress with pharmacotherapy for alcohol-dependent individuals; however, there remains a critical need for the development of novel and additional therapeutic approaches. Alcohol and nicotine are commonly abused together, and there is evidence that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in both alcohol and nicotine dependence. Varenicline, a partial agonist at the alpha4beta2 nAChRs, reduces nicotine intake and was recently approved as a smoking cessation aid. We have investigated the role of varenicline in the modulation of ethanol consumption and seeking using three different animal models of drinking. We show that acute administration of varenicline, in doses reported to reduce nicotine reward, selectively reduced ethanol but not sucrose seeking using an operant self-administration drinking paradigm and also decreased voluntary ethanol but not water consumption in animals chronically exposed to ethanol for 2 months before varenicline treatment. Furthermore, chronic varenicline administration decreased ethanol consumption, which did not result in a rebound increase in ethanol intake when the varenicline was no longer administered. The data suggest that the alpha4beta2 nAChRs may play a role in ethanol-seeking behaviors in animals chronically exposed to ethanol. The selectivity of varenicline in decreasing ethanol consumption combined with its reported safety profile and mild side effects in humans suggest that varenicline may prove to be a treatment for alcohol dependence. IS - 30 JF - Proceedings of the National Academy of Sciences of the USA AD - selenab@gallo.ucsf.edu EP - 12523 TI - Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking VL - 104 SP - 12518 KW - acetylcholine KW - alcohol KW - animals KW - champix KW - nicotine KW - pharmacotherapy KW - varenicline AU - Steensland, P AU - Simms, JA AU - Holgate, J AU - Richards, JK AU - Bartlett, SE PY - 2007/07/11/ UR - http://dx.doi.org/10.1073/pnas.0705368104 ER -