3/16/2023 0 Comments Hedonic set point alcohol![]() ![]() We have recently adapted an intermittent access two-bottle choice model that was first described in the 1970s ( Amit et al, 1970 Wise, 1973), and have shown that rats will consume 20% ethanol without the use of sucrose fading or water deprivation ( Nielsen et al, 2008 Simms et al, 2008 Steensland et al, 2007). ![]() The addition of these sweetened solutions may introduce a confound to studies exploring ethanol-reinforced behaviors. Others have found that sucrose may cause similar brain activation and be more rewarding to rodents than drugs that are commonly abused by humans, such as opioids ( Spangler et al, 2004) and cocaine ( Lenoir et al, 2007). In addition, there is emerging evidence that indicates that sucrose may be addictive in rodents ( Avena et al, 2008 Colantuoni et al, 2002). These methods lead to high ethanol consumption while the sucrose is present but drinking drops precipitously once the sweetener is removed ( Carrillo et al, 2008 Koob and Weiss, 1990 Samson, 1986 Samson et al, 1999). Ethanol is added later to these sweetened solutions and the sucrose/saccharin is gradually faded out until the animal is pressing for an unsweetened, dilute ethanol solution. Using this method, animals are trained to lever press in operant chambers by shaping with sweetened solutions (sucrose or saccharin). Since its introduction in the mid-1980s, sucrose fading has largely been adopted as the primary means of getting rats to acquire operant ethanol self-administration ( Samson, 1986). However, this model suffers from several limitations, including the need for sucrose fading and water deprivation to initiate drinking behavior, and low baseline ethanol consumption in outbred rat strains following removal of these initiation procedures. The operant model has had an important role in the preclinical validation and characterization of the two medications approved by the US Food and Drug Administration for the treatment of alcohol use disorders (AUDs) since 1994: naltrexone (ReVia) ( Bienkowski et al, 1999 Burattini et al, 2006 Dayas et al, 2007 Holter and Spanagel, 1999 Katner et al, 1999 Le et al, 1999 Liu and Weiss, 2002) and acamprosate (Campral) ( Bachteler et al, 2005 Czachowski et al, 2001 Heyser et al, 1998 Holter et al, 1997 Rassnick et al, 1992). This model has been invaluable in the alcohol research field, as it has enabled researchers to explore the motivational aspects of ethanol seeking in rodents, with the use of fixed and progressive ratio schedules and reinstatement paradigms. The operant self-administration paradigm is a commonly used model in which animals are trained to lever press for ethanol reinforcement ( Samson et al, 1988). The current standard models of ethanol-seeking behaviors use rodents in a variety of paradigms that relate to various aspects of consumption and relapse. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. In addition, training history (20% ethanol vs 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than did animals trained to consume 10% ethanol with a sucrose fade (1.5 vs 0.7 g/kg every 30 min) and reached significantly higher blood ethanol concentrations. ![]() With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3–6 g/kg every 14 h) without the use of a sucrose-fading procedure. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: (1) intermittent (Monday, Wednesday, and Friday) or (2) daily (Monday through Friday). In this study, we have adapted the model to an operant self-administration paradigm. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5–6 g/kg every 24 h vs 2–3 g/kg every 24 h, respectively). A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. ![]()
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