Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access.
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.
Larson
Erin B
EB
Department of Psychiatry, University of Texas Southwestern Medical Center, Texas, USA.
Anker
Justin J
JJ
Gliddon
Luke A
LA
Fons
Kyah S
KS
Carroll
Marilyn E
ME
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage* / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology* / Q000502:physiology; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D012727:Sex Characteristics
D004967:Estrogens; D011372:Progestins; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; D003042:Cocaine