Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse

Abstract

One of the major challenges in preclinical studies of alcohol abuse and dependence remains the development of paradigms that will elicit high ethanol intake and mimic the progressive transition from low or moderate social drinking to excessive alcohol consumption. Exposure of outbred rats to repeated cycles of free-choice ethanol intake and withdrawal with the use of intermittent access to 20% ethanol in a 2-bottle choice procedure (IA2BC) has been shown to induce a gradual escalation of voluntary ethanol intake and preference, eventually reaching ethanol consumption levels of 5-6 g/kg/24 h, and inducing pharmacologically relevant blood ethanol concentrations (BECs). This procedure has recently been gaining popularity due to its simplicity, high validity, and reliable outcomes. Here we review experimental and methodological data related to IA2BC, and discuss the usefulness and advantages of this procedure as a valuable pre-training method for initiating operant ethanol self-administration of high ethanol intake, as well as conditioned place preference (CPP). Despite some limitations, we provide evidence that IA2BC and related operant procedures provide the possibility to operationalize multiple aspects of alcohol abuse and addiction in a rat model, including transition from social-like drinking to excessive alcohol consumption, binge drinking, alcohol seeking, relapse, and neuroadaptations related to excessive alcohol intake. Hence, IA2BC appears to be a useful and relevant procedure for preclinical evaluation of potential therapeutic approaches against alcohol abuse disorders.

Keywords: Animal models; Binge drinking; Blood ethanol concentrations; Ethanol; Excessive drinking; Intermittent access; Neuroadaptations; Operant self-administration; Relapse; Two-bottle choice.

Figure 1. Pattern of ethanol intake and BECs during a 30-min operant 20% ethanol self-administration session

A. Number of 20% ethanol deliveries during 10-min intervals. The graph summarizes data collected and published in Carnicella et al., 2008 and Neasta et al., 2011; n = 15. B. Correlations between BECs and the ethanol consumed by 20% ethanol IA2BC-trained rats during a 30-min operant 20% ethanol self-administration session (black, n = 12), or by rats pre-trained with a sucrose-fading 10% ethanol procedure, during a 1-h operant 10% ethanol self-administration session (gray, n = 10).