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

• Published in: Psychopharmacology 2014-09, Vol.231 (18), p.3787-3798
• Main Authors: Zlebnik, Natalie E., Saykao, Amy T., Carroll, Marilyn E.
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-2 Receptor Antagonists - pharmacology; Animal behavior; Animals; Biomedical and Life Sciences; Biomedicine; Cocaine; Cocaine - administration & dosage; Cocaine abuse; Cues; Dopamine Uptake Inhibitors - administration & dosage; Dosage and administration; Drug addiction; Drug therapy; Drug-Seeking Behavior - drug effects; Exercise; Extinction, Psychological - drug effects; Female; Health aspects; Male; Motor Activity - drug effects; Neurosciences; Original Investigation; Pharmacology/Toxicology; Physical Conditioning, Animal - physiology; Progesterone; Progesterone - pharmacology; Psychiatry; Rats; Rats, Wistar; Rodents; Running - physiology; Self Administration; Yohimbine - pharmacology
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-014-3513-6

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.