Effects of progesterone on the reinstatement of cocaine-seeking behavior in female rats.
Estradiol benzoate (EB) facilitates the acquisition and reinstatement of cocaine-seeking behavior when administered to ovariectomized (OVX) rats. In contrast, progesterone (P) decreases acquisition of cocaine self-administration, but the effects of P on the reinstatement of drug seeking are not known. The purpose of the present study was to compare the effects of EB and P on the reinstatement of cocaine-seeking behavior in female rats. Rats received either OVX or sham surgery (SH) and were trained to lever press for intravenous cocaine infusions (0.4 mg/kg) under a fixed ratio 1, 20-s time-out schedule during daily 2-hr sessions. After 14 days of stable responding, saline replaced cocaine, and a 21-day extinction period began. After extinction, rats were separated into 5 treatment groups (OVX+EB, OVX+EB+P, OVX+vehicle [VEH], SH+P, or SH+VEH), and VEH, EB, or EB+P was administered 30 min prior to each session for 5 days. After 3 days of hormone treatment, rats received a saline or cocaine (10 mg/kg) injection, and reinstatement of lever responding was assessed. Reinstatement responding in the OVX+EB group was greater relative to the OVX+EB+P, SH+P, and OVX+VEH groups, which had low levels of cocaine-primed responding. The SH+VEH and OVX+EB groups displayed similar high levels of cocaine-elicited reinstatement. The suppression of cocaine-induced reinstatement following P treatment suggests a role for P in the prevention of relapse to cocaine self-administration in female cocaine users.
Anker
Justin J
JJ
Department of Psychiatry, Division of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. anke0022@umn.edu
Larson
Erin B
EB
Gliddon
Luke A
LA
Carroll
Marilyn E
ME
D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism / Q000503:physiopathology*; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D007262:Infusions, Intravenous; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology* / Q000502:physiology; D011372:Progestins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D012055:Reinforcement Schedule; D012646:Self Administration
D004967:Estrogens; D011372:Progestins; C074283:estradiol 3-benzoate; D011374:Progesterone; D004958:Estradiol; D003042:Cocaine