Prenatal inhibition of hypothalamic sex steroid uptake by cocaine: effects on neurobehavioral sexual differentiation in male rats.
Several adrenergically active drugs have been shown to prevent the masculinizing and/or defeminizing effects of testosterone on brain sexual differentiation. We examined the ability of the neuronal norepinephrine uptake blocker, cocaine, to produce similar effects. The ability of cocaine to inhibit sex steroid incorporation into the hypothalamus during a critical period for sexual differentiation of the brain was examined in females treated at birth with testosterone. Sixty minutes after administration, cocaine was observed to inhibit both testosterone and estradiol incorporation into the hypothalamus by approximately 50%. Long-term consequences of prenatal cocaine exposure were studied by injecting Sprague-Dawley dams twice daily with 3, 10 or 30 mg/kg of cocaine hydrochloride on days 15 through 20 of gestation and examining the offspring. In adulthood, cocaine-exposed males, but not females were found to exhibit significantly less marking behavior than controls. Cocaine-exposed males in the 10 mg/kg group tested for sex behavior exhibited demasculinization in some aspects of the behaviors tested. Measurement of plasma hormone levels in this group revealed elevated levels of plasma LH, but normal levels of FSH and testosterone. No differences were observed in cocaine-exposed males with respect to sex organ or adrenal weights, but thymus was approximately 25% smaller compared to control males at 80 days of age. In a separate experiment, dams were treated with 3 mg/kg of cocaine twice daily from days 15 through 21 of gestation and half of the male pups received additional injections twice a day for the first 5 days postnatally.(ABSTRACT TRUNCATED AT 250 WORDS)
Raum
W J
WJ
U.C.L.A. and Harbor/U.C.L.A. Medical Center, Department of Medicine, Torrance 90509.
McGivern
R F
RF
Peterson
M A
MA
Shryne
J H
JH
Gorski
R A
RA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D004958:Estradiol / Q000493:pharmacokinetics* / Q000502:physiology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013739:Testosterone / Q000493:pharmacokinetics* / Q000502:physiology
D013739:Testosterone; D004958:Estradiol; D003042:Cocaine