• Y-maze;
  • periadolescent rats;
  • chronic amphetamine;
  • novelty exploration;
  • CREB;
  • hippocampus;
  • CA1–3

Background and purpose:

We investigated possible differences in the impact of chronic amphetamine administration during adolescence and adulthood on aspects of behaviour and brain chemistry.

Experimental approach:

Adult (n=32) and adolescent (n=32) male Sprague–Dawley rats were given either D-amphetamine sulphate (10 mg kg−1 daily, i.p.) or saline (1 mL kg−1, i.p.) for 10 days. Rats were subsequently tested for anxiety-like behaviour, learning and memory, and sensorimotor gating. Nine weeks later, rats received saline (1 mL kg−1) or acute amphetamine challenge (1.5 mg kg−1) and the expression levels of mRNA for tyrosine kinase B (TrkB) or cAMP response element-binding protein (CREB) were measured in the hippocampus.

Key results:

The adolescent amphetamine pretreated group revealed a deficit in exploration on the Y-maze during a 6 h retention test. The frequency of visits to the novel arm was 35% lower for the amphetamine group compared with controls. In parallel, a 43% decrease in hippocampal CREB mRNA, but not TrkB mRNA, was observed in periadolescent rats treated chronically with amphetamine 9 weeks earlier. None of the effects were detected in the adult treated cohort.

Conclusions and implications:

Chronic amphetamine treatment during periadolescence resulted in altered behaviour on the Y-maze and persistent downregulation of hippocampal CREB mRNA expression. Given that this group had intact spatial learning and reference memory, it would appear that the deficits observed on the Y-maze reflect a dysfunction in response to novelty. Because no effects of amphetamine treatment were observed in the adult cohort, these data suggest idiosyncratic sensitivity of periadolescence to the long-term effects of psychostimulants.

British Journal of Pharmacology (2008) 154, 417–428; doi:10.1038/bjp.2008.126