Effects of RU 486 and tamoxifen on cocaine-induced behavioral and endocrinologic activations in male and female Fischer rats.
Evidence suggests that sex differences in response to cocaine administration may be regulated by activation of progesterone and estrogen receptors. To test this hypothesis, rats were pretreated with either RU 486 (progesterone antagonist; 0, 3, or 25 mg/kg), tamoxifen (estrogen antagonist; 0, 1, or 3 mg/kg), or vehicle followed by saline or cocaine administration (15 mg/kg). Although RU 486 did not affect cocaine-induced locomotor activity in female rats, it dose-dependently decreased such activity in males (3 mg/kg significantly attenuated locomotor responses in cocaine-treated rats as compared with vehicle treatment or 25 mg/kg of RU 486). RU 486 also affected baseline serum levels of corticosterone. Males treated with 3 mg/kg of RU 486 plus cocaine had higher progesterone and corticosterone serum levels than vehicle-treated groups. In females, both doses (3 and 25 mg/kg) of RU 486 significantly attenuated corticosterone serum levels compared with vehicle treatment. For both sexes overall, tamoxifen neither significantly influenced cocaine-induced ambulatory and rearing responses nor altered cocaine-induced progesterone and corticosterone serum levels. Taken together, our results suggest that progesterone receptors have a sexually dimorphic role in cocaine-induced effects, but estrogen receptors have only a limited role. Moreover, both receptor antagonists modulate neurochemical responses differentially.
Wu
Hui-Bing Katie
HB
Department of Psychology, Hunter College, Biopsychology and Behavioral Neuroscience PhD Subprogram of the Graduate Center, The City University of New York, New York, New York 10021, USA.
Niyomchai
Tipyamol
T
Festa
Eugene
E
Minerly
AnaChristina E
AE
Weierstall
Karen
K
Hunter
Deirtra
D
Sun
Weilun
W
Weiner
Jan
J
Jenab
Shirzad
S
Quinones-Jenab
Vanya
V
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000097:blood / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000494:pharmacology*; D011374:Progesterone / Q000097:blood; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors; D013629:Tamoxifen / Q000494:pharmacology*
D006727:Hormone Antagonists; D013629:Tamoxifen; D015735:Mifepristone; D011374:Progesterone; D003042:Cocaine; D003345:Corticosterone