GABA receptor systems have long been implicated in alcoholism, and GABAergic drugs have demonstrated efficacy in altering alcohol intake in some rodent models. The present study was designed to assess the effects of baclofen, muscimol, and gaboxadol (THIP) in a variation on a new mouse model of binge-like ethanol intake. Three hours into their dark cycle, male and female C57BL/6J mice were given access to a 20% unsweetened ethanol solution for 2 h each day, for four days. On day five, mice received varying doses of baclofen, muscimol or THIP and were allowed access to 20% ethanol for 60 min. Baclofen dose-dependently increased binge-like ethanol intake, while both muscimol and THIP reduced ethanol intake. Subsequent studies testing the effect of baclofen, muscimol and THIP on water intake using the same procedure revealed that whereas baclofen had no significant effect, muscimol and THIP both reduced the measure. These results add to the growing literature suggesting a role for GABA receptor systems in the modulation of ethanol intake. However, whereas the role of GABA(B) receptor systems seems selective in the modulation of binge-like ethanol intake, the role for GABA(A) receptor systems appears to also extend to general fluid intake.

Background There is considerable research examining differences in adolescent and adult sensitivity and tolerance to ethanol related behavioral phenotypes. However, the available published data has almost exclusively assessed these behaviors in outbred rats. The present study was conducted using the alcohol preferring inbred mouse strain C57BL/6J (B6) and the alcohol non-preferring inbred mouse strain DBA/2J (D2) to determine if differences in the sedative and ataxic effects of ethanol exist between adolescents and adults, and to determine whether there are any genetic influences involved therein. Methods Adolescent and adult mice of each sex and genotype were given intraperitoneal (i.p.) injections of ethanol (1.5, 1.75 or 4.0 g/kg) or saline and assessed for the loss of righting reflex (LORR) or hind footslips on the balance beam apparatus. These animals were then tested for the development of tolerance to these behaviors on subsequent days. Results Despite evident pharmacokinetic differences, D2 adults were found to be relatively more sensitive than their adolescent D2 counterparts in addition to B6 animals of both age groups. Furthermore, although adult animals appeared to develop significantly greater degrees of tolerance to ethanol-induced hypnosis compared to adolescents, these effects are likely in part related to differences in ethanol absorption/metabolism across time. Taking into account pharmacokinetic differences and the overall poor performance of male adults, adolescent animals were found to be equally if not more sensitive to the motor incoordinating (ataxic) effects of ethanol. Overall, tolerance to these effects varied by age and genotype but appeared to be related to changes in ethanol pharmacokinetics rather than strict behavioral sensitivity. Conclusion The current work suggests that adolescent B6 and D2 inbred mice exhibit ontogenetic differences in sensitivity to ethanol’s hypnotic and ataxic effects. Importantly, in some cases age differences emerge as a function of differential ethanol pharmacokinetics. These results extend the current literature examining this critical developmental period in mice and illustrate the benefits of comparing ethanol related developmental differences in different genetic mouse populations.

Rationale-Repeated exposure to many abused drugs produces a progressive increase in locomotor sensitivity, referred to as locomotor sensitization. Locomotor sensitization may persist for some time following termination of repeated drug administration, and contextual learning appears to facilitate expression of the behavioral phenomenon. However, relatively little is known about the persistence of and the degree to which contextual learning influences locomotor sensitization to alcohol (ethanol).Objectives-The goal of the present work was determine the duration of locomotor sensitization to ethanol and the degree to which contextual learning positively influences the induction, expression, and persistence of the behavioral phenomenon in DBA/2J mice.Methods-Sensitized (with or without ethanol-paired exposure to the testing chamber)and nonsensitized saline control mice were left undisturbed in their home cages until subsequent ethanol challenge and testing in the locomotor activity testing chambers 7, 14, 21, 28, 42, 56, and/or 70 days after cessation of the ethanol sensitization procedure. Retro-orbital sinus bloods were sampled to determine whether the sensitization procedure had altered blood ethanol clearance rates.Results-Locomotor sensitization persisted through post-sensitization day 14, and contextual learning prolonged the expression of this phenomenon through at least post-sensitization day 28. Blood ethanol concentrations did not differ in any experiment.Conclusions-Locomotor sensitization to ethanol persists for some time after cessation of repeated ethanol exposure and the association of contextual cues with the ethanol experience lengthens this persistence. The present data lay the groundwork for investigations into the neuroadaptive changes that underlie locomotor sensitization to ethanol in mice.