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Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
Methamphetamine-alcohol interactions in murine models of sequential and simultaneous oral drug-taking
Elissa K Fultz1, Douglas L Martin1, Courtney N Hudson1
1Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA.
Background:
A 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.
Methods:
In one study, mice with a 10-day history of binge alcohol-drinking [5,10, 20 and 40% (v/v); 2h/day] were trained to self-administer oral MA in an operant-conditioning paradigm (10-40mg/L). In a second study, mice with a 10-day history of limited-access oral MA-drinking (5, 10, 20 and 40mg/L; 2h/day) were presented with alcohol (5-40% v/v; 2h/day) and then a choice between solutions of 20% alcohol, 10mg/L MA or their mix.
Results:
Under 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 10mg/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.
Discussion:
These 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.
Insights
Prior alcohol exposure decreased methamphetamine reinforcement but increased intake when available non-contingently. Methamphetamine history increased alcohol consumption, highlighting complex drug-drug interactions in co-use models.
Area of Science:
- Neuroscience
- Addiction Research
- Behavioral Pharmacology
Background:
- High comorbidity exists between methamphetamine (MA) addiction and alcohol use disorders.
- Sequential and simultaneous MA-alcohol mixing increases the risk of co-abuse.
- Limited preclinical research exists on the biobehavioral interactions between MA and alcohol in drug-taking behaviors.
Purpose of the Study:
- To investigate how prior histories of MA or alcohol consumption influence the intake of the other drug.
- To utilize simple murine models of voluntary oral drug consumption to examine MA-alcohol interactions.
- To explore the biobehavioral underpinnings of MA-alcohol co-abuse.
Main Methods:
- Mice with a 10-day history of binge alcohol drinking were trained to self-administer oral MA.
- Mice with a 10-day history of limited-access oral MA drinking were presented with alcohol and then a choice between alcohol, MA, or their mix.
- Operant-conditioning paradigms and voluntary oral drug consumption models were employed.
Main Results:
- Alcohol-drinking mice showed less MA reinforcement under operant-conditioning but consumed more MA and preferred it when availability was not behaviorally contingent.
- Prior MA-drinking history increased alcohol intake across various concentrations.
- These findings reveal distinct influences of prior drug history on subsequent drug intake.
Conclusions:
- Simple murine models can effectively study sequential and simultaneous MA-alcohol mixing.
- These models are relevant for advancing the biobehavioral understanding of MA-alcohol co-abuse.
- Prior exposure to one drug significantly alters the intake and reinforcement of the other.
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