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.

Subgroup-dependent effects of voluntary alcohol intake on behavioral profiles in outbred Wistar rats

“…The alcohol-drinking animals were introduced to alcohol using an intermittent two-bottle free-choice paradigm, modified from Wise [20] and Wayner [21], and summarized by Carnicella et al [22]. On Tuesdays, Wednesdays, and Thursdays every week, the rats were given 24 h access to one bottle of water and one bottle of 20% alcohol (v/v).…”

“…We here introduce a free-choice intermittent access paradigm modified from the models used by Wise [20] and Wayner [21], summarized by Carnicella et al [22]. The animals had free access to 20% alcohol and water during three consecutive days followed by a four-day intermission with access to water only.…”

The Novel μ-Opioid Receptor Antagonist GSK1521498 Decreases Both Alcohol Seeking and Drinking: Evidence from a New Preclinical Model of Alcohol Seeking

“…The commonly used strains of laboratory rats do not readily drink high quantities of alcohol unless sweet taste (eg, sucrose) fading techniques are used to induce it (see, eg, Samson, 1986;Czachowski and Samson, 2002), or animals are exposed intermittently to alcohol for a prolonged period of time under two-or three-bottle choice procedures (Wise, 1973;Simms et al, 2008;Carnicella et al, 2014), or are first made dependent by exposing them for long periods to alcohol in vapor chambers to induce drinking in withdrawal (Koob, 2013).…”

Neuropeptide Receptors as Treatment Targets in Alcohol Use Disorders

“…However, this method does not address the motivational and reinforcing processes that regulate alcohol-intake and seeking, which are also critical in the development of addiction. Thus we used the operant selfadministration procedure to evaluate potential shifts in motivational behavior induced by the IA procedure to better model what occurs during the development of AUD in humans (285,318). We found that previous experience with operant alcohol selfadministration before IA two-bottle free choice preference drinking resulted in a faster acquisition of alcohol self-administration after the IA procedure and significantly increased lever-pressing for alcohol during self-administration compared to the non-IA controls (Figure 8 A-D).…”

“…Bottles can be available either under continuously or under an IA schedule. IA drinking has been shown to escalate consumption faster and higher compared to continuous access drinking (285,286). Concentrations of alcohol between 10-20% (v/v) have been used.…”