Low doses of amphetamine lead to immediate and lasting locomotor sensitization in adolescent, not adult, male rats

Abstract

Although there is much evidence for age differences in behavioural responses to psychostimulants in rats, the differential, lasting impact of drug exposures has rarely been investigated using direct comparisons of adolescent and adult rats. Male rats were pre-treated with 0.5 mg/kg amphetamine or saline on either postnatal days (P) 31 and P33 or P76 and P78, and locomotor activity was measured for 1 h. Adolescent, and not adult, rats showed a significant increase in distance traveled from the first to second pre-treatment. There was no evidence of sensitization of locomotor activity in either adolescents or adults on Challenge 1 to the same dose of amphetamine when tested 12 days later on P45 (late adolescence) or on P90. Rats that were pre-treated as adolescents exhibited locomotor sensitization to 1.5 mg/kg amphetamine as adults (P60) on Challenge 2, 27 days after pre-treatment, particularly in the group that had also received amphetamine on Challenge 1 at P45. Rats that were pre-treated as adults did not show sensitization on Challenge 2. The results suggest that the rapid adaptations to drug exposures in adolescence have greater consequences than identical treatment in adulthood, and highlight the unique vulnerability of adolescents to brief, low dose drug exposure.