Estrogen and progesterone affect cocaine pharmacokinetics in female rats.
Several studies have reported sex differences in behavioral responses to cocaine whereby females display a greater degree of locomotor activity. Fluctuations in estrogen and progesterone during the estrous cycle have been postulated to underlie these behavioral differences. In this study, we tested the hypothesis that hormonal replacement (estrogen or progesterone) in ovariectomized rats affects cocaine pharmacokinetics. We found that estrogen replacement did not affect cocaine-induced locomotor activity, but progesterone attenuated locomotor counts in comparison with control groups receiving only sesame oil. Estrogen, however, decreased brain levels of cocaine and norcocaine 30 min after cocaine administration in comparison to the group-receiving vehicle at that time point. In addition, in progesterone-treated rats, levels of benzoylecgonine and ecgonine methylester were higher at 30 min post-administration than at 15 min. No changes were found in blood levels of the metabolites. These findings suggest that while progesterone has an impact on locomotor behavior, pharmacokinetic effects may have a limited role in mediating behavioral responses to cocaine.
Niyomchai
Tipyamol
T
Department of Psychology, Hunter College of the City University of New York, 695 Park Ave., New York, NY 10021, USA.
Akhavan
Alaleh
A
Festa
Eugene D
ED
Lin
Shen-Nan
SN
Lamm
Lolita
L
Foltz
Rodger
R
Quiñones-Jenab
Vanya
V
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D013058:Mass Spectrometry / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D010052:Ovariectomy / Q000379:methods; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D004967:Estrogens; C008671:norcocaine; D011374:Progesterone; C005618:benzoylecgonine; D003042:Cocaine; C034524:ecgonine methyl ester