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.

Relatively short periods of passive IG infusion of ethanol induced levels of ethanol self-infusion in genetically heterogeneous rats that were comparable with drinking intakes previously reported in rats selectively bred for ethanol intake/preference. Although the induction of dependence/withdrawal may have played a role in this outcome, an alternative interpretation is that experimental rats self-infused more ethanol because passive exposure produced tolerance to aversive pharmacological effects that would otherwise limit intake of the paired flavor because of development of conditioned taste aversion. The current findings provide a strong basis for future work designed to identify parametric determinants of this form of self-administration, its sensitivity to genetic influences, and its neurobiological substrates.

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Three experiments used the Intragastric Alcohol Consumption (IGAC) procedure to examine effects of variations in passive ethanol exposure on withdrawal and voluntary ethanol intake in two inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2). Experimental treatments were selected to induce quantitative differences in ethanol dependence and withdrawal severity by: (a) varying the periodicity of passive ethanol exposure (3, 6 or 9 infusions/day), (b) varying the dose per infusion (Low, Medium or High), and (c) varying the duration of passive exposure (3, 5 or 10 days). All experiments included control groups passively exposed to water. B6 mice generally self-infused more ethanol than D2 mice, but passive ethanol exposure increased IGAC in both strains, with D2 mice showing larger relative increases during the first few days of ethanol access. Bout data supported the characterization of B6 mice as sippers and D2 mice as gulpers. Three larger infusions per day produced a stronger effect on IGAC than six or nine smaller infusions, especially in D2 mice. Increased IGAC was strongly predicted by cumulative ethanol dose and intoxication during passive exposure in both strains. Withdrawal during the passive exposure phase was also a strong predictor of increased IGAC in D2 mice. However, B6 mice showed little withdrawal, precluding analysis of its potential role. Overall, these data support the hypothesis that dependence-induced increases in IGAC are jointly determined by two processes that might vary across genotypes: (a) tolerance to aversive post-absorptive ethanol effects, and (b) negative reinforcement (i.e., alleviation of withdrawal by self-administered ethanol).

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