Varenicline Reduces Alcohol Intake During Repeated Cycles of Alcohol Reaccess Following Deprivation in Alcohol‐Preferring (P) Rats

Abstract

Background Most alcoholics experience periods of voluntary alcohol abstinence or imposed alcohol deprivation followed by a return to alcohol drinking. The current study examined whether varenicline (VAR) reduces alcohol intake during a return to drinking after periods of alcohol deprivation in rats selectively bred for high alcohol drinking (the alcohol preferring or “P” rats). Methods Alcohol-experienced P rats were given 24-hour access to food and water and scheduled access to alcohol (15% and 30% v/v) for 2 h/d. After 4 weeks, rats were deprived of alcohol for 2 weeks, followed by reaccess to alcohol for 2 weeks, and this pattern was repeated for a total of 3 cycles. Rats were fed either vehicle (VEH) or VAR, in doses of 0.5, 1.0 or 2.0 mg/kg BW, at 1 hour prior to onset of the daily alcohol reaccess period for the first 5 days of each of the 3 alcohol reaccess cycles. Results Low dose VAR (0.5 mg/kg BW) reduced alcohol intake during the 5 days of drug treatment in alcohol reaccess cycles 1 and 2. Higher doses of VAR (1.0 mg/kg BW and 2.0 mg/kg BW) reduced alcohol intake during the 5 days of treatment in all 3 alcohol reaccess cycles. The decrease in alcohol intake disappeared with termination of VAR treatment in all alcohol reaccess cycles. Conclusions The results demonstrate that VAR decreases alcohol intake during multiple cycles of alcohol reaccess following alcohol deprivation in rats and suggests that it may prevent a return to heavy alcohol drinking during a lapse from alcohol abstinence in humans with AUD.

Co‐Administration of Low‐Dose Naltrexone and Bupropion Reduces Alcohol Drinking in Alcohol‐Preferring (P) Rats

“…NTX and BUP, expressed as free base masses, were added to the gelatin solution to provide the following doses: 10.0 mg of NTX/3.0 ml solution/kg BW, 10.0 mg or 20.0 mg BUP/3.0 ml solution/kg BW, and 10.0 mg NTX + 10.0 mg BUP/3.0 ml solution/kg BW. While still hot, the gelatin solution containing the drug(s) was aliquoted into star shaped molds with the volume of each aliquot determined by the final concentration of the gelatin (mg drug/ml of gelatin solution) and the BW of the animal in order to produce individual drug doses, 1 dose per day per rat, as previously described (Froehlich et al, 2013a, 2013b, 2016, 2017a, 2017b).…”

“…In our early work, drugs were delivered via injection and the duration of drug treatment was necessarily short. In order to reduce the stress of drug administration, and allow for prolonged drug treatment, we developed an oral drug delivery approach for rodents that is analogous to the way that drugs are delivered to humans (Froehlich et al, 2013a, 2013b, 2016, 2017a, 2017b; Rasmussen et al, 2015).…”

Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats

“…However, some studies examining Var and EtOH intake appear to conflict with the present findings. For example, treatment with 2 mg/kg Var reduced EtOH self-administration to ~1.5 g/kg/2-hour session following scheduled access and repeated cycles of deprivation (Froehlich et al 2016(Froehlich et al , 2017Czachowski et al, 2018). A number of factors contribute to these differences.…”

An improved model of ethanol and nicotine co-use in female P rats: Effects of naltrexone, varenicline, and the selective nicotinic α6β2* antagonist r-bPiDI

“…Nevertheless, the varenicline-induced decrease in nicotine intake observed here is consistent with previous preclinical results (Funk et al, 2016; Maggio et al, 2018; Scuppa et al, 2015). Although several preclinical studies have shown decreases in EtOH consumption following pretreatment with varenicline (Czachowski et al, 2018; Froehlich et al, 2017; Steensland et al, 2007), those studies only examined EtOH consumption in the absence of nicotine. Overall, preclinical evidence provides limited support for varenicline’s efficacy as a pharmacotherapeutic for co-users of EtOH and nicotine.…”