Strain-dependent behavioural sensitization to amphetamine: role of environmental influences

Repeated daily pairings of 1mg/kg of amphetamine and test environment induced a large, significant increase of locomotion in mice of the C57BL/6 strain, while a slight, non-significant increase was observed in mice of the DBA/2 strain. Neither C57BL/6 nor DBA/2 mice showed behavioral sensitization to amphetamine in the test cages when the drug was repeatedly administered in their home cage. Moreover, C57BL/6 but not DBA/2 mice showed conditioned hyperactivity. Subsequently six daily pairings of saline and test cage produced a slight, non-significant reduction of the hyperactive response shown by C57BL/6 mice, accompanied by a further increase in the behavioural effect of amphetamine. Finally, a similar, significant context-independent sensitization (unpaired vs control) was observed in mice of the two strains subjected to pairings of saline with the test cage; while context-dependent sensitization (paired vs unpaired) was observed only in C57BL/6 mice. Naive DBA/2 were less susceptible than C57BL/6 mice to the behavioural effect of high doses of amphetamine. However, effects of the low dose of amphetamine used in this experiment did not show strain differences in naive mice. These results show that C57BL/6 are more susceptible than DBA/2 mice to context-dependent behavioural sensitization to amphetamine. Moreover, they suggest that neither conditioned hyperactivity nor context-independent sensitization account for strain differences in environment-specific behavioural sensitization.