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

John R. Smethells, Natashia L. Swalve, Lynn E. Eberly, Marilyn E. Carroll

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29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2999-3008
Number of pages10
JournalPsychopharmacology
Volume233
Issue number15-16
DOIs
StatePublished - Aug 1 2016

Bibliographical note

Funding Information:
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).

Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.

Keywords

  • Cocaine
  • Delay discounting
  • Female
  • Impulsive choice
  • Rats
  • Recreational drug use

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