Persistent downregulation of hippocampal CREB mRNA parallels a Y-maze deficit in adolescent rats following semi-chronic amphetamine administration
Article first published online: 29 JAN 2009
2008 British Pharmacological Society
British Journal of Pharmacology
Special Issue: Special Issue: Neuropharmacology of Addiction
Volume 154, Issue 2, pages 417–428, May 2008
How to Cite
Featherby, T., Van Den Buuse, M., Lubman, D. I. and Lawrence, A. J. (2008), Persistent downregulation of hippocampal CREB mRNA parallels a Y-maze deficit in adolescent rats following semi-chronic amphetamine administration. British Journal of Pharmacology, 154: 417–428. doi: 10.1038/bjp.2008.126
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received February 26, 2008, Accepted February 4, 2008)
- periadolescent rats;
- chronic amphetamine;
- novelty exploration;
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.
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.
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