Regulation of Operant Oral Ethanol Self-Administration: A Dose-Response Curve Study in Rats

Abstract

Background-Oral ethanol self-administration procedures in rats are useful pre-clinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation of the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored due to the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In the present study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats.

Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice

“…The most likely explanation is that the mice (temporarily) reduce their ethanol consumption due to the negative/aversive effects produced by repetitive daily binge-like ethanol consumption prior to the development of tolerance. Supporting this possibility, Carnicella and colleague demonstrated a u-shaped ethanol dose response curve in rats' lever pressing for access to ethanol (Carnicella, Yowell, & Ron, 2011). Specifically, the rats progressively increased their response for ethanol until the ethanol concentration reached 10-20%, and as the concentration increased beyond this point, their responding progressively decreased.…”

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

“…Conducting the CPP experiment in rats with a history of excessive ethanol (via IA2BC training) provides a more behaviorally relevant way to habituate the animals to ethanol. Furthermore, we showed that similar habituation to ethanol via IA2BC training leads to high ethanol consumption in an operant self-administration procedure (Barak et al, 2013; Carnicella et al, 2008; Carnicella, Yowell, & Ron, 2011) (see below).…”

“…Animals consuming less than 4 g/kg/24 h at the baseline are excluded from the study (Carnicella et al, 2008; Carnicella et al, 2011), as they are considered resilient to excessive alcohol intake. Exclusion of rats according to this predefined criterion is critical as rats drinking low levels of ethanol in the IA2BC do not acquire operant 20% ethanol self-administration (S. Carnicella, unpublished observation).…”

“…Then, operant sessions are conducted 5 days per week, with the schedule requirement increased to FR3 and the length of session shortened from 60 to 30 min over the first 2 weeks, as we found that the majority of rats terminate their operant activity after 30 min (Carnicella et al, 2008). One month of training under these parameters (FR3, 30 min), usually results in a stable baseline of operant ethanol self-administration (Barak, Carnicella, et al, 2011; Barak et al, 2013; Carnicella et al, 2011). Animals pressing for less than 0.4 g/kg/30 min at the baseline are excluded from the study (Carnicella et al, 2011).…”

“…One month of training under these parameters (FR3, 30 min), usually results in a stable baseline of operant ethanol self-administration (Barak, Carnicella, et al, 2011; Barak et al, 2013; Carnicella et al, 2011). Animals pressing for less than 0.4 g/kg/30 min at the baseline are excluded from the study (Carnicella et al, 2011). The operant responding criterion is standard for most operant procedures, including ethanol operant self-administration using sucrose-fading pre-training (e.g., Bertholomey, Verplaetse, & Czachowski, 2013; McCool & Chappell, 2009; Radwanska et al, 2008; Simms, Bito-Onon, Chatterjee, & Bartlett, 2010).…”