Abstract
Rationale
Rats categorized as high responders (HR) based on their activity in an inescapable novel environment self-administer more amphetamine than low responder (LR) rats. Previous research has also demonstrated that novel stimuli presented during the amphetamine self-administration session decreases the number of infusions earned.
Objectives
This study determined whether individual differences in response to inescapable or free-choice novelty differentially predict the ability of novel stimuli to decrease amphetamine self-administration. Further, this study determined whether novel stimuli maintained the ability to reduce self-administration with repeated presentations, and whether the effect of novel stimuli varied as a function of the unit dose of amphetamine tested.
Methods
Male rats were screened for their response in inescapable and free-choice novelty tests. Following initial training using a high unit dose of amphetamine (0.1 mg/kg per infusion), the dose was reduced (0.03 mg/kg per infusion), and novel stimuli were presented in the operant conditioning chamber on four separate sessions. In experiment 2, novel stimuli were presented during several sessions at a variety of amphetamine doses (0.003, 0.01, 0.03, and 0.056 mg/kg per infusion).
Results
Four repeated presentations of novel stimuli reduced amphetamine self-administration with no significant loss in the effect of novel stimuli across repeated presentations. In experiment 2, novel stimuli reduced amphetamine self-administration at low unit doses (0.003 mg/kg and 0.01 mg/kg per infusion), and rats classified as HR based on their activity in inescapable novel stimuli were more disrupted by novel stimuli than LR rats.
Conclusions
These results suggest that repeated presentation of novel stimuli can reduce amphetamine self-administration at low unit doses and that HR rats are more sensitive than LR rats to non-drug stimuli that compete with responding for amphetamine.
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Acknowledgements
Research was funded by USPHS grant P50 DA05312. M.E.C. was supported by USPHS grant F32 DA16013. C.M.S. was supported by Summer Research and Creativity Grant at the University of Kentucky. The authors would like to thank Justin Dixon, William Dotson, and Nathan Gilbertson for their assistance with this project.
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Cain, M.E., Smith, C.M. & Bardo, M.T. The effect of novelty on amphetamine self-administration in rats classified as high and low responders. Psychopharmacology 176, 129–138 (2004). https://doi.org/10.1007/s00213-004-1870-2
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DOI: https://doi.org/10.1007/s00213-004-1870-2