Fultz Elissa K, Martin Douglas L, Hudson Courtney N, Kippin Tod E, Szumlinski Karen K
Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106-9660, USA.
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.
Drug Alcohol Depend. 2017 Aug 1;177:178-186. doi: 10.1016/j.drugalcdep.2017.03.026. Epub 2017 May 24.
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.
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.
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.
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.
甲基苯丙胺（MA）成瘾与酒精使用障碍之间存在高度共病现象，MA与酒精先后使用及同时混合使用都会增加共同滥用的风险。由于临床前研究很少关注在药物摄取行为背景下MA与酒精之间的生物行为相互作用，我们采用简单的自愿口服药物消费小鼠模型，以研究MA或酒精服用史如何影响另一种药物的摄入量。
在一项研究中，对有10天暴饮酒精史（5%、10%、20%和40%（体积/体积）；每天2小时）的小鼠进行训练，使其在操作性条件反射范式（10 - 40毫克/升）下自行口服MA。在第二项研究中，给有10天有限接触口服MA史（5毫克/升、10毫克/升、20毫克/升和40毫克/升；每天2小时）的小鼠提供酒精（5% - 40%体积/体积；每天2小时），然后让它们在20%酒精溶液、10毫克/升MA溶液或它们的混合物之间进行选择。
在操作性条件反射程序下，与饮水对照小鼠相比，饮酒小鼠总体上对MA的强化反应较少。然而，当药物可得性不取决于行为时，饮酒小鼠比未接触过药物和同时接触过两种药物的小鼠摄入更多的MA，并且对10毫克/升MA溶液表现出更大的偏好。相反，先前的MA饮用史会增加在一系列酒精浓度下的酒精摄入量。
这些探索性研究表明，采用程序简单的小鼠模型来研究MA与酒精先后及同时口服混合的情况是可行的，这对于推进我们对MA - 酒精共同滥用的生物行为理解具有重要意义。
