Drinking Levels and Profiles of Alcohol Addicted Rats Predict Response to Nalmefene

Pharmacotherapeutic options supporting the treatment of alcohol dependence are recommended and available but underutilized, partly due to questions about efficacy. Nalmefene, a μ-opioid receptor antagonist and partial kappa receptor agonist, is recommended for reduction of alcohol consumption, but evidence about its effectiveness has been equivocal; identifying factors which predict response will help optimize treatment. The alcohol deprivation effect paradigm is a tightly controlled procedure comprising repeated deprivation and reintroduction phases, leading to increased preference for alcohol; reintroduction approximates relapse. Using a digital drinkometer system measuring high-resolution drinking behavior, we examined the effects of nalmefene on relapse drinking behavior in alcohol addicted rats. We also tested whether drinking behavior in the relapse phase prior to nalmefene administration predicted treatment response. We further examined whether longitudinal drinking behavior and locomotor activity predicted treatment response. Our results showed that nalmefene (0.3 mg/kg) reduced relapse-like consumption significantly (∼20%) compared to vehicle on the first 2 days of alcohol reintroduction. Examining the first 6 h of a preceded treatment-free relapse episode revealed drinking patterns clustering the rats into responders (reduction of >40%, = 17) and non-responders (reduction of