Intermittent ethanol access schedule in rats as a preclinical model of alcohol abuse.
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.
Inserm U836, Grenoble Institut des Neurosciences, Dynamique et Physiopathologie des Ganglions de la Base, Grenoble, France; Université de Grenoble, France.
Sebastien
S
Carnicella
The Gallo Research Center, Department of Neurology, University of California, San Francisco, USA.
Dorit
D
Ron
School of Psychological Sciences and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: barakseg@post.tau.ac.il.
Segev
S
Barak
D000222:Adaptation, Physiological; D000223:Adaptation, Psychological; D000428:Alcohol Drinking / Q000523:psychology*; D000437:Alcoholism / Q000523:psychology*; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012646:Self Administration; D013045:Species Specificity
D000431:Ethanol
Animal models; Binge drinking; Blood ethanol concentrations; Ethanol; Excessive drinking; Intermittent access; Neuroadaptations; Operant self-administration; Relapse; Two-bottle choice