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Alterations in executive functioning induced by repeated amphetamine exposure Whelan, Jennifer M.

Abstract

Chronic exposure to psychostimulants such as amphetamine (AMPH) can induce long-term disruptions in cognition via actions on prefrontal cortex dopamine. Previous work has shown that two types of executive functions, set shifting and working memory (WM), are disrupted by AMPH sensitization and that these cognitive domains are impaired in schizophrenics and stimulant abusers. We assessed the effects of AMPH sensitization on behavioural flexibility using a cross-maze set shifting task and a WM task using the delayed spatial win-shift (SWSh) task in Long Evans (LE) and Sprague Dawley (SD) rats. Rats were exposed to an AMPH sensitization regimen (15 AMPH or saline injections: 1-5 mg/kg every 2nd day, increasing the dose by 1 mg every 3rd injections) following habituation on the mazes. In experiment 1, LE and SD rats were initially trained on a visual cue discrimination. During the set shift, rats were required to shift from the previously acquired visual-cue-based strategy to a response strategy (e.g.; always turn left, ignore the visual cue). For the reversal, rats were trained to reverse their turn direction. AMPH treatment did not impair learning of the initial cue discrimination in either strain. However, AMPH treated rats learned the response discrimination faster than controls during the set shift and AMPH treated LE rats were faster than controls to reach acquisition criterion during the response reversal. AMPH treatment neither impaired nor improved reversal learning in SD rats. In experiment 2, rats were tested on the SWSh task in which spatial information acquired during a training phase was used 30 minutes later during the testing phase in order to retrieve food pellets on the maze. In this task, AMPH treated rats were faster to re-attain criterion than control rats. Correlational analysis further revealed that AMPH sensitized rats that required more days to reach criterion before AMPH treatment (i.e. slow learners) tended to make more errors during re-acquisition of the memory task. Viewed collectively, these results suggest that chronic AMPH treatment can enhance behavioural flexibility and WM assessed in this manner. However, repeated AMPH exposure may have exacerbated pre-existing cognitive deficits in slow learning rats.

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