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

Abstract

Background: This study examined whether combining naltrexone (NTX) with bupropion (BUP) is more effective in reducing alcohol drinking in alcohol-preferring (P) rats with a genetic predisposition toward high voluntary alcohol intake than either drug alone.

Methods: Alcohol-experienced, adult, male, P rats were fed NTX alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 10.0 mg/kg BW, BUP alone in a dose of 20.0 mg/kg BW, NTX (10.0 mg/kg BW) + BUP (10.0 mg/kg BW), or vehicle (VEH) at 1 hour prior to onset of a daily 2-hour alcohol access period for 5 consecutive days.

Results: When administered alone, neither NTX (10.0 mg/kg BW) nor BUP, in either of 2 doses (10.0 mg/kg BW or 20.0 mg/kg BW), reduced voluntary alcohol intake in P rats. However, NTX combined with BUP (10.0 mg/kg NTX + 10.0 mg/kg BUP) and given as a single medication significantly reduced alcohol consumption throughout prolonged treatment.

Conclusions: Combining low doses of NTX and BUP, each of which is ineffective when given alone, increases the efficacy of the medication. Low drug doses circumvent the problem of negative side effects that can occur with higher doses of either drug. A reduction in side effects can facilitate patient compliance and improve clinical outcomes for alcoholics and heavy drinkers who want to reduce their alcohol intake. The results, together with those from our prior studies, demonstrate the strength of a combinatorial pharmacotherapeutic approach to the treatment of alcohol use disorder.

Keywords: Alcohol Drinking; Alcohol Treatment; Bupropion; Naltrexone; Selectively Bred Rats.

Figure 1

(A) Effect of naltrexone (NTX), alone and in combination with bupropion (BUP), on alcohol intake on each of 5 days of drug treatment in P rats. (B) Effect of NTX, alone and in combination with BUP, on mean alcohol intake over the 5 days of drug treatment. Each point represents the mean ± SEM. ** p<0.01, vs VEH.