Effects of combined exercise and progesterone treatments on cocaine seeking in male and female rats

Natalie E. Zlebnik, Amy T. Saykao, Marilyn E. Carroll

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Background: Individually, both treatment with progesterone and concurrent access to an exercise wheel reduce cocaine self-administration under long-access conditions and suppress cocaine-primed reinstatement in female rats. In the present study, wheel running and progesterone (alone and combined) were assessed for their effects on reinstatement of cocaine-seeking primed by yohimbine, cocaine, and cocaine-paired cues. Methods: Male and female rats were implanted with an intravenous catheter and allowed to self-administer cocaine (0.4 mg/kg/inf, iv) during 6-h sessions for 10 days. Subsequently, the groups of male and female rats were each divided into two groups that were given concurrent access to either a locked or unlocked running wheel under extinction conditions for 14 days. Next, all four groups were tested in a within-subjects design for reinstatement of cocaine-seeking precipitated by separate administration of cocaine-paired stimuli, yohimbine, or cocaine or the combination of yohimbine+cocaine-paired stimuli or cocaine+cocaine-paired stimuli. These priming conditions were tested in the presence of concurrent wheel access (W), pretreatment with progesterone (P), or both (W+P). Results: In agreement with previous results, females responded more for cocaine than males during maintenance. Additionally, concurrent wheel running attenuated extinction responses and cocaine-primed reinstatement in females but not in males. Across all priming conditions, W+P reduced reinstatement compared to control conditions, and for cocaine-primed reinstatement in male rats, the combined W+P treatment was more effective than W or P alone. Conclusion: Under certain conditions, combined behavioral (exercise) and pharmacological (progesterone) interventions were more successful at reducing cocaine-seeking behavior than either intervention alone.

Original languageEnglish (US)
Pages (from-to)3787-3798
Number of pages12
Issue number18
StatePublished - Sep 2014

Bibliographical note

Funding Information:
Role of funding source Funding for this study was provided by the National Institute on Drug Abuse (NIDA) grant R01 DA003240 (MEC); NIDA had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication.

Funding Information:
Acknowledgments This research was supported by NIDA grant R01 DA003240 (MEC). The authors would like to thank Yosef Amrami, Tom Baron, Katie Bressler, Alex Claxton, Nathan Holtz, Danielle Johansson, Seth Johnson, Aneal Rege, and Tyler Rehbein for technical assistance and Krista Walkowiak, DVM, for veterinary care.


  • Addiction
  • Cocaine
  • Exercise
  • Progesterone
  • Reinstatement
  • Relapse
  • Sex differences

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