Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access

Exp Clin Psychopharmacol. 2007 Oct;15(5):461-71. doi: 10.1037/1064-1297.15.5.461.


Estrogen increases and progesterone decreases the acquisition and reinstatement of cocaine-seeking behavior in female rats. Here estrogen and progesterone were studied for their effects on the escalation of cocaine self-administration in female rats. The rats received ovariectomy (OVX) or sham (SH) surgery and were treated with estradiol benzoate (0.05 mg/kg sc) and/or progesterone (0.5 mg/kg) or vehicle (indicated by E, P, and V), resulting in 5 groups: SH+V, SH+P, OVX+V, OVX+E, OVX+E+P. Rats self-administered intravenous cocaine (0.4 mg/kg) under a fixed ratio 1 (FR 1) schedule during 2-hr sessions and were then given 6-hr sessions (long access; LgA) (FR 1) for 21 days. After LgA, self-administration was reassessed with 2-hr sessions under the FR 1 and a progressive ratio schedule with 4 cocaine doses. There were no differences among the 5 groups in cocaine self-administration during initial 2-hr sessions. During LgA, the SH+V, OVX+E, and OVX+V groups escalated their cocaine self-administration, whereas the OVX+E+P and SH+P groups did not. Estradiol increased escalation in the OVX+E group compared with the OVX+V group, and progesterone (SH+P) reduced escalation compared with the SH+V group. When estrogen and progesterone were both administered in OVX rats (OVX+E+P), escalation was significantly lower than in the OVX+E group. Cocaine infusions during the 2-hr sessions were significantly higher after escalation than before in all groups except the progesterone-treated groups (SH+P and OVX+E+P). Estrogen promoted and progesterone inhibited escalation of cocaine self-administration, illustrating the importance of female gonadal hormones in drug-seeking behavior.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage*
  • Cocaine / pharmacology
  • Cocaine-Related Disorders / physiopathology
  • Cocaine-Related Disorders / psychology
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • Estradiol / physiology
  • Estrogens / pharmacology*
  • Female
  • Ovariectomy
  • Progesterone / pharmacology*
  • Progesterone / physiology
  • Progestins / pharmacology*
  • Rats
  • Rats, Wistar
  • Self Administration
  • Sex Characteristics


  • Estrogens
  • Progestins
  • estradiol 3-benzoate
  • Progesterone
  • Estradiol
  • Cocaine