Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning
Résumé
Behaviorally sensitizing regimen of amphetamine exposure has diverse effects on learning, memory and cognition that is likely to be a consequence of long term neural adaptations occurring in the cortico-limbic-striatal circuitry. In particular, altered dopamine signaling in the nucleus accumbens and medial prefrontal cortex has been implicated to underlie amphetamine-induced changes in behavior. The present study sought to test the hypothesis that repeated amphetamine exposure disrupts the regulation of limbic information processing and the balance of competing limbic control over appetitive behaviour. Mice received 7 intra-peritoneal injections of d-amphetamine (2.5mg/kg or 5mg/kg) or vehicle solution (saline) and were trained in a 1) simultaneous conditioned cue and place preference task using a 6 arm radial maze, found to depend upon the integrity of the hippocampus (HPC), and basolateral amygdala (BLA) respectively and a 2) conditional BLA-dependent cue-, and HPC-dependent place learning task using an elevated T-maze. In both tasks, the vehicle pre-treatment group acquired cue learning first, followed by the emergence of significant place/spatial learning. In contrast, pre-treatment with repeated amphetamine caused marked deviations from normal acquisition patterns of place and cue conditioning, significantly facilitating HPC-dependent place conditioning in the first task, while attenuating BLA-dependent cue conditioning in both tasks. These findings provide the first demonstration of aberrant regulation of HPC and BLA-dependent learning as a result of amphetamine exposure, highlighting the importance of the meso-coticolimbic dopamine system in maintaining the balance of limbic control over appetitive behavior.
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