Intragastric self-infusion of ethanol in high- and low-drinking mouse genotypes after passive ethanol exposure

Abstract

Two experiments examined the effect of 5 days of passive exposure to ethanol (or water) on later self-infusion of ethanol or water via surgically implanted intragastric (IG) catheters in mouse genotypes previously shown to drink high (C57BL/6J, HAP2) or low (DBA/2J, LAP2) amounts of ethanol in home-cage continuous-access two-bottle choice procedures. Intragastric ethanol selfinfusion was affected by both genotype and a history of passive ethanol exposure, with greater intakes in the high-drinking genotypes and in groups that received passive exposure to ethanol. Passive ethanol exposure also increased preference for the flavor that signaled ethanol infusion (S+), eliminating genetic differences in this measure. The increases in ethanol intake and S+ preference induced by ethanol exposure might have been mediated jointly by development of tolerance to aversive post-absorptive ethanol effects and negative reinforcement because of alleviation of withdrawal. Bout analyses indicated that ethanol exposure increased ethanol selfinfusion by increasing the total number of daily bouts rather than by increasing bout size. These analyses also showed that DBA/2J mice infused larger ethanol bouts and a greater percentage of their total intakes in large bouts than C57BL/6J mice. Overall, these studies suggest that the IG self-infusion procedure is a potentially useful new tool for studying genetic and environmental influences on excessive ethanol intake and preference in mice.

Operant ethanol self-administration in ethanol dependent mice

“…Of particular interest, the study involved using this model to examine ethanol self-administration in mouse inbred strains that exhibit high (C57BL/6J) versus low (DBA/2J) ethanol preference, as well as mouse lines selectively bred for high (HAP2) versus low (LAP2) ethanol preference. Increased ethanol self-administration in the model was demonstrated in all mice, whether they typically exhibit high (C57BL/6J, HAP2) or low (DBA/2J, LAP2) ethanol intake under baseline conditions (Fidler et al, 2011). Thus, intragastric self-administration of ethanol was similar for all genotypes after a period of forced ethanol infusions even though these genotypes greatly differ in their acceptance of ethanol when it is presented for oral consumption.…”

“…As in the case for rats, studies have shown mice to respond for ethanol as a positive reinforcer when it is delivered orally (Meisch, 2001), intravenously (Grahame & Cunningham, 1997), and directly into the stomach via intragastric infusion (Fidler et al, 2011). While early studies showed that ethanol responding and intake is enhanced in food-deprived mice (Middaugh & Kelley, 1999), ethanol was demonstrated to be an effective positive reinforcer in non-food deprived mice as well (Ford, Fretwell, Mark, & Finn, 2007; Middaugh, Lee, & Bandy, 2000).…”

“…Finally, a valuable feature of using mice in these studies is that it more readily facilitates examination of genetic contributions to operant ethanol self-administration behavior. Indeed, several studies have examined ethanol self-administration involving operant conditioning procedures in various genetic mouse models, including different inbred strains (Fidler et al, 2011; Grahame & Cunningham, 1997; Risinger et al, 1998), mice selectively bred for other ethanol-related phenotypes (Ford et al, 2011), and several genetically manipulated models engineered to be deficient in various target proteins (knockout models) (Grahame, Low, & Cunningham, 1998; Olive, Mehmert, Messing, & Hodge, 2000; Risinger, Doan, & Vickrey, 1999; Roberts et al, 2001; Roberts, McDonald, et al, 2000). Thus, while rats have been the predominant choice of species for operant ethanol self-administration studies, a growing body of literature indicates that operant conditioning procedures can be effectively employed in studying ethanol self-administration behavior in mice.…”

“…This was followed by a 4-day choice phase in which mice were given a choice to drink from the bottle with a flavor that produces ethanol infusions or a second bottle with a different flavor that resulted in water infusions. Results indicated that forced intragastric infusions of ethanol resulted in increased self-administration of ethanol in both the no-choice and choice phases of the experiment (Fidler et al, 2011). Of particular interest, the study involved using this model to examine ethanol self-administration in mouse inbred strains that exhibit high (C57BL/6J) versus low (DBA/2J) ethanol preference, as well as mouse lines selectively bred for high (HAP2) versus low (LAP2) ethanol preference.…”

“…More recently, studies in animals with a history of dependence (chronic but ‘forced’ ethanol exposure and withdrawal) have demonstrated that ethanol can serve as a potent negative reinforcer as well. For example, increased ethanol self-administration was shown in studies where dependence was induced by chronic administration of ethanol in a nutritionally fortified liquid diet (that served as the animals’ sole source of calories and fluid) (Brown, Jackson, & Stephens, 1998; Chu, Koob, Cole, Zorilla, & Roberts, 2007; Gilpin et al, 2009; Schulteis, Hyytiä, Heinrichs, & Koob, 1996), via intragastric infusions (Cunningham, Fidler, Murphy, Mulgrew, & Smitasin, 2013; Fidler et al, 2011; Fidler et al, 2012), and via inhalation of alcohol vapors (e.g., Becker & Lopez, 2004; Rimondini, Arlinde, Sommer, & Heilig, 2002; Roberts, Heyser, Cole, Griffin, & Koob, 2000). In such studies, the altered physiological state associated with dependence along with the capacity for ethanol to alleviate withdrawal symptoms is posited to not only sustain ethanol self-administration, but also promote escalation of intake (Becker, 2008; Becker, 2013; Heilig, Egli, Crabbe, & Becker, 2010).…”