Effect of short- vs. long-term estrogen on reinstatement of cocaine-seeking behavior in female rats

Erin B. Larson, Megan E. Roth, Justin J. Anker, Marilyn E. Carroll

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74 Scopus citations


Estrogen effects on cocaine-induced reinstatement of lever responding were examined in sham-operated, vehicle-treated (SH + VEH), ovariectomized (OVX + VEH), and OVX female Wistar rats with estrogen replacement (OVX + EB). The effect of long- (64 ± 1.56 days) and short-term (9 days) EB treatment on reinstatement of cocaine-seeking behavior was compared in Experiment 1 and 2, respectively, in order to compare the effect of EB when it was present during the development vs. expression of reinstatement of cocaine-seeking behavior. Rats were trained to self-administer 0.4 mg/kg/inf cocaine. After the acquisition criteria were met, rats continued to respond for cocaine for 2 h/day for a 14-day maintenance period. Cocaine was then replaced with saline and the 21-day extinction period commenced. Subsequently, rats were tested for reinstatement of lever responding on the previously drug-paired lever after alternating daily injections of saline or cocaine. In both experiments, there were no differences between groups in self-administration behavior during training, maintenance, or extinction. In Experiment 1, SH + VEH and chronically treated OVX + EB rats had greater cocaine-induced reinstatement than OVX + VEH rats. In Experiment 2, short-term treated OVX + EB rats also showed enhanced cocaine-induced reinstatement compared to OVX + VEH rats. The results indicate that EB-mediated enhancement of cocaine-induced reinstatement is dependent on EB presence during the expression of reinstatement but not during the formation of stimulus-reward associations during the development of cocaine-reinforced behavior.

Original languageEnglish (US)
Pages (from-to)98-108
Number of pages11
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Sep 2005

Bibliographical note

Funding Information:
The authors would like to thank Paula Whitten, Sarah Nelson, and Jon German for their technical assistance in conducting the experiments, and Jennifer Perry for her critical review of the manuscript. This research was supported by NIDA R01 DA03240, K05 DA 15267 (MEC), and T32 DA07097, F31 DA14161 (MER).


  • Cocaine
  • Estrogen
  • Female
  • Reinstatement
  • Self-administration


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