Rationale Varenicline a smoking-cessation agent may be useful in treating alcohol use disorders. and whether varenicline alters sensitivity to alcohol in rats trained to discriminate a moderate alcohol dose (1 Benidipine hydrochloride g/kg IG) vs. water. Second animals trained to self-administer alcohol underwent assessments to test the effects of: (i) varenicline (0 0.3 1 3 mg/kg IP) on self-administration (ii) alcohol priming (0 0.3 1 g/kg IG) on self-administration and seeking behavior (iii) varenicline (1 mg/kg) in combination with alcohol priming (1 g/kg) on these behaviors. Results Varenicline did not substitute for alcohol but disrupted the expression of sensitivity to alcohol. Varenicline decreased self-administration but only at a motor impairing dose (3 mg/kg). Alcohol priming decreased self-administration and seeking behavior. Varenicline (1 mg/kg) blocked this effect under self-administration conditions but not seeking conditions which effectively resulted in increased alcohol intake. Conclusions These findings suggest the importance of further behavioral and mechanistic studies to evaluate the use of varenicline in treating alcohol use disorders and its potential impact on drinking patterns in smokers using varenicline as a smoking cessation aid. Keywords: alcoholism Chantix ethanol nicotine priming reinstatement drinking Introduction Alcohol use disorders are a continuing world-wide public health issue. For this reason there is great interest in better understanding behaviors that lead to excessive drinking and developing effective treatments for reducing ongoing drinking and preventing relapse. To date the US Food and Drug Administration (FDA)-approved treatments for alcohol dependence are naltrexone (opioid antagonist) disulfiram (aldehyde dehydrogenase inhibitor) and acamprosate (actions on GABA and glutamate). These compounds have different mechanisms of action and each have demonstrated efficacy in a limited subset of the patient population (Liang and Olsen 2014). However there is continued emphasis on developing novel Benidipine hydrochloride therapeutics and investigating potential novel pharmacological targets for the treatment of alcohol use disorders (AUDs). One target that has been receiving increased attention is the nicotinic acetylcholine system. This is of particular interest given that clinical studies show high comorbidity between smoking and heavy drinking (~80% of heavy drinkers also smoke) and that heavy drinking may influence nicotine dependence (Chatterjee and Bartlett 2010; Benidipine hydrochloride Dani and Harris 2005; Falk et al. 2006; Benidipine hydrochloride Grant 1998; McKee et al. 2007). For this reason there has been growing interest in the pharmacological compound varenicline for the treatment of AUDs. Varenicline is currently FDA-approved for use as a smoking cessation agent (Cahill et al. 2012) and is a partial nicotinic acetylcholine receptors (nAChRs) agonist at α4β2 α3β2 and α6 and a full agonist at α3β4 and α7 nAChRs (Coe et al. 2005; Rollema et al. Rabbit Polyclonal to MRPL44. 2009). In clinical studies varenicline has been shown to have efficacy in decreasing alcohol craving and consumption particularly in smokers (Fucito et al. 2011; Mitchell et al. 2012). Additionally evidence from human nonhuman primates and rodent studies have shown that varenicline may also be useful in decreasing alcohol consumption and alcohol-seeking behaviors (Childs et al. 2012; Feduccia et al. 2014; Hendrickson et al. 2010; Kaminski and Weerts 2014; Litten et al. 2013; McKee et al. 2009; Mitchell et al. 2012; Steensland et al. 2007; Benidipine hydrochloride Wouda et al. 2011). Importantly varenicline appears to selectively attenuate alcohol-related behaviors as compared to naltrexone (Steensland et al. 2007). An important consideration when studying factors that influence drinking and relapse is the influence of Benidipine hydrochloride the pharmacological effects of alcohol on these behaviors specifically the role of alcohol priming (e.g. alcohol pre-exposure leading to additional alcohol consumption or increased craving). Numerous medical studies have proven that alcoholic beverages priming not merely raises craving in alcoholics (Hodgson et al. 1979; Ludwig and Wikler 1974) but.