Role of genotype in the development of locomotor sensitization to alcohol in adult and adolescent mice: comparison of the DBA/2J and C57BL/6J inbred mouse strains

Abstract

Background: Animal models that explore differential sensitivity to the effects of acute and repeated exposure of alcohol (ethanol) may be influenced by both the developmental and genetic profile of the population. Therefore, we sought to compare the influence of ontogeny on sensitivity to ethanol-induced locomotor stimulation and on the induction of locomotor sensitization to this effect across 2 inbred strains of mice; the ethanol consuming C57BL/6J and the ethanol avoiding DBA/2J strains. Methods: C57BL/6J and DBA/2J adults (postnatal day [PD] 60 to 80) and adolescents (PD 30±2) were assessed for basal activity, acute response to 2.0 g/kg ethanol, and the expression of locomotor sensitization following repeated administration of 2.5, 3.0, or 3.5 g/kg ethanol. Results: Basal activity was different across development for the C57BL/6J, but not DBA/2J, with adult B6 mice showing persistently greater baseline activity. Adolescents of both strains were more sensitive than adults to acute ethanol-induced locomotor stimulation; adults exhibited a decrease in their acute response across the testing session. Adolescent DBA/2J mice developed less ethanol sensitization compared to adults, with significant sensitization observed only following repeated administration of the lowest ethanol dose (2.5 g/kg), whereas DBA/2J adults sensitized to all doses. Age did not influence the development of ethanol sensitization for the C57BL/6J strain, as both adults and adolescents displayed a sensitized response following all ethanol doses. Conclusions: These results suggest that the developmental pattern of locomotor sensitivity to ethanol is unique to the genotypic profile of the animal model.