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The present experiment examined ethanol self-administration in C57BL/6J (C57) and DBA/2J (DBA) mice using a continuous access operant procedure. Adult male C57 and DBA mice were initially trained to perform a lever press response to obtain access to 10% w/v sucrose solution. Subsequently, the mice were placed in operant chambers on a continuous (23 hr/day) basis with access to food (FR1), 10% v/v ethanol (FR4), and water from a sipper tube. C57 mice displayed greater rates of responding on the ethanol-associated lever compared with DBA mice. Responding on the food lever was the same in both strains, but DBA mice consumed greater amounts of water. C57 mice consistently displayed both prandial and nonprandial episodes (bouts) of ethanol responding. DBA mice did not respond for ethanol in bouts. Following 50 consecutive sessions, ethanol concentration was altered every 5 days. Response patterns were determined using 0, 5, 10, 20, and 30% v/v ethanol concentrations. C57 mice displayed concentration-dependent responding on the ethanol lever showing that ethanol was functioning as an effective reinforcer in this strain. In contrast, responding on the ethanol lever by DBA mice did not change as a function of ethanol concentration. Saccharin (0.2% w/v) was subsequently added to the ethanol mixture, and responding was examined at 0, 5, 10, and 20% ethanol concentrations. Overall, ethanol lever responding was increased in both strains. As before, C57 mice showed higher levels of ethanol responding, compared with DBA mice. C57 mice also showed higher responding for saccharin alone. These results are consistent with findings that suggest orally administered ethanol is a more effective reinforcer in C57 mice than in DBA mice. Furthermore, C57 mice engage in ethanol-reinforced responding over a broader range of conditions than DBA mice.

Various serotonergic receptor systems are thought to influence the motivational effects of ethanol. This experiment characterized the acquisition of ethanol-induced conditioned taste aversion and ethanol-induced conditioned place reference in mutant knockout mice lacking 5-HT1b receptors. In the taste conditioning procedure, adult homozygous knockout mice (-/-) and homozygous wild-type mice (+/+) received access to 0.2 M NaCl solution, followed immediately by intraperitoneal injection of 0 to 4 g/kg of ethanol. Ethanol produced dose-dependent conditioned taste aversion that was the same in both genotypes. In the place conditioning procedure, knockout and wild-type mice received six pairings of a tactile stimulus with ethanol (2 g/kg, i.p.). A different tactile stimulus was paired with saline. Ethanol produced increases in locomotor activity, with wild-type mice showing higher levels of ethanol-stimulated activity than knockout mice during conditioning trials 5 and 6. Wild-type mice demonstrated conditioned place preference for the ethanol-paired stimulus. In contrast, knockout mice showed no evidence of place conditioning. These results are generally consistent with an important role for serotonergic systems in ethanol reward and specifically indicate that 5-HT1b receptors are important for ethanol's rewarding effects but not for ethanol's aversive effects.

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