Elissa K Fultz1, Douglas L Martin1, Courtney N Hudson1, Tod E Kippin2, Karen K Szumlinski3. 1. Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA. 2. Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA; Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA; Institute for Collaborative Biotechnology, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA. 3. Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA; Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA. Electronic address: karen.szumlinski@psych.ucsb.edu.
Abstract
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.
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.
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