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Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone

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Abstract

Rationale

Impulsive choice, or an inability to delay immediate gratification, has been strongly linked to the development and persistence of drug abuse. Indeed, delaying drug use itself may underlie drug addiction and relapse. Thus, employing treatments that are efficacious in reducing impulsive choice (atomoxetine; ATO) or drug-seeking behavior (progesterone; PRO) may be an effective means of treating drug addiction.

Objective

The current study assessed sex differences in the effects of PRO, ATO, and their combination in a delay discounting paradigm for cocaine and for sucrose pellets.

Method

Male and female rats chose between a small-immediate or a large-delayed (0, 7.5, 15, 30, 60 s) outcome in an impulsive choice procedure for sucrose pellets (1 vs. 3 pellets) or for iv cocaine infusions (0.3 vs. 0.9 mg/kg). Following baseline assessment of impulsive choice, rats received daily treatment of vehicle (VEH), PRO (0.5 mg/kg), ATO (1.5 mg/kg), or a combination (PRO + ATO) until a second assessment of impulsive choice was determined.

Results

Compared to the VEH group, females were less impulsive for cocaine following PRO or the PRO + ATO combined treatment, whereas males were less impulsive for cocaine following ATO. No treatment effects were observed on impulsive choice for sucrose pellets.

Conclusions

The present results indicate that impulsive choice for cocaine is reduced by PRO in females and by ATO in males. These findings suggest both treatments may be an effective intervention in treating cocaine abuse, but that their effectiveness differs by sex.

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Acknowledgments

We would like to thank Dr. Natalie Zlebnik for her thoughtful contributions, Seth Johnson for technical assistance, and lastly Jared Mitchell and Heather Veghlan for assisting in conducting this research. This study was supported by NIH/NIDA P50 DA033942 (MEC [PI] and LEE) and a NIDA training grant T32 DA007097 (JRS; Thomas Molitor—PI).

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Authors and Affiliations

  1. Department of Psychiatry, University of Minnesota, Minneapolis, MN, 55455, USA

    John R. Smethells, Natashia L. Swalve & Marilyn E. Carroll

  2. Division of Biostatistics, University of Minnesota, Minneapolis, MN, 55455, USA

    Lynn E. Eberly

Authors
  1. John R. Smethells
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  2. Natashia L. Swalve
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  3. Lynn E. Eberly
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  4. Marilyn E. Carroll
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Correspondence to John R. Smethells.

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The experimental protocol was approved by the University of Minnesota Institutional Animal Care and Use Committee and conducted in compliance with the Guide for the Care and Use of Animals.

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Smethells, J.R., Swalve, N.L., Eberly, L.E. et al. Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone. Psychopharmacology 233, 2999–3008 (2016). https://doi.org/10.1007/s00213-016-4345-3

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  • DOI: https://doi.org/10.1007/s00213-016-4345-3

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