Persistent downregulation of hippocampal CREB mRNA parallels a Y-maze deficit in adolescent rats following semi-chronic amphetamine administration.
OBJECTIVE
We investigated possible differences in the impact of chronic amphetamine administration during adolescence and adulthood on aspects of behaviour and brain chemistry.


METHODS
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.


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
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.
Featherby
T
T
Brain Injury and Repair Group, Howard Florey Institute, University of Melbourne, Parkville, Victoria, Australia.
van den Buuse
M
M
Lubman
D I
DI
Lawrence
A J
AJ
D000367:Age Factors; D000661:Amphetamine / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004334:Drug Administration Schedule; D005106:Exploratory Behavior / Q000187:drug effects*; D006185:Habituation, Psychophysiologic; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D013216:Reflex, Startle / Q000187:drug effects; D012741:Sexual Maturation; D013997:Time Factors
D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D000661:Amphetamine; D020813:Receptor, trkB