Methamphetamine-alcohol interactions in murine models of sequential and simultaneous oral drug-taking

- A binge-drinking history reduced methamphetamine reinforcement and intake in mice.
- However, binge-drinking increased methamphetamine preference under free-access.
- Conversely, oral methamphetamine intake augmented home-cage alcohol-drinking.
- Simple oral drug-taking procedures are useful to model drug-alcohol co-abuse in mice.

BackgroundA high degree of co-morbidity exists between methamphetamine (MA) addiction and alcohol use disorders and both sequential and simultaneous MA-alcohol mixing increases risk for co-abuse. As little preclinical work has focused on the biobehavioral interactions between MA and alcohol within the context of drug-taking behavior, we employed simple murine models of voluntary oral drug consumption to examine how prior histories of either MA- or alcohol-taking influence the intake of the other drug.MethodsIn one study, mice with a 10-day history of binge alcohol-drinking [5,10, 20 and 40% (v/v); 2 h/day] were trained to self-administer oral MA in an operant-conditioning paradigm (10-40 mg/L). In a second study, mice with a 10-day history of limited-access oral MA-drinking (5, 10, 20 and 40 mg/L; 2 h/day) were presented with alcohol (5-40% v/v; 2 h/day) and then a choice between solutions of 20% alcohol, 10 mg/L MA or their mix.ResultsUnder operant-conditioning procedures, alcohol-drinking mice exhibited less MA reinforcement overall, than water controls. However, when drug availability was not behaviorally-contingent, alcohol-drinking mice consumed more MA and exhibited greater preference for the 10 mg/L MA solution than drug-naïve and combination drug-experienced mice. Conversely, prior MA-drinking history increased alcohol intake across a range of alcohol concentrations.DiscussionThese exploratory studies indicate the feasibility of employing procedurally simple murine models of sequential and simultaneous oral MA-alcohol mixing of relevance to advancing our biobehavioral understanding of MA-alcohol co-abuse.