Progesterone receptors activation after acute cocaine administration.
Cocaine modulates serum levels of progesterone in intact female and male rats, as well as in pregnant dams, and progesterone decreases or attenuates cocaine-induced behavioral and reward responses. It has been postulated that cocaine's modulation of serum progesterone levels may in turn alter progesterone receptor activity, thereby contributing to cocaine-induced alterations of neuronal functions and genomic regulations. To test this hypothesis, intact male rats received acute injections of saline or cocaine (15 or 30 mg/kg, dissolved in 0.9% saline, intraperitoneal). Progesterone serum levels, progesterone receptor (PR) protein levels, and PR-DNA binding complexes were measured in the striatum by radioimmunoassay, Western blot, and gel shift analyses, respectively. After injection of 15 mg/kg of cocaine, induction of progesterone serum levels was closely followed by an increase in receptor protein levels and DNA binding complexes. After injection of 30 mg/kg of cocaine, similar effects were observed along with an attenuation of receptor protein levels and DNA binding complexes at 60 min. Our results suggest that activation of progesterone receptors may be a mechanism by which cocaine mediates behavior through molecular alterations in the central nervous system.
Wu
Hui-Bing K
HB
Department of Psychology, Hunter College, City University of New York, New York, NY 10021, USA.
Fabian
Sosimo
S
Jenab
Shirzad
S
Quiñones-Jenab
Vanya
V
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D008297:Male; D011374:Progesterone / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011980:Receptors, Progesterone / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D004268:DNA-Binding Proteins; D018765:Dopamine Uptake Inhibitors; D011980:Receptors, Progesterone; D011374:Progesterone; D003042:Cocaine