Cocaine disrupts estrous cyclicity and alters the reproductive neuroendocrine axis in the rat.
Although a common drug of abuse, cocaine's effects on cyclic reproductive functions and the neuroendocrine systems regulating these functions have not been studied. Here, we report the effects of cocaine on (1) estrous cyclicity and ovulation rates and (2) the stimulated in vitro release of hypothalamic GnRH and aminergic neurotransmitters directly involved in regulating or modulating GnRH release. Within 7 days of treatment with 10 mg kg-1 day-1 of cocaine HCl subcutaneously, rats demonstrated significant estrous cycle irregularity including repetitive days of estrus and prolonged periods of diestrus. After 6 weeks of treatment, cocaine-treated rats exhibited a 44.3% decrease in ovulation rates. For the in vitro studies, bilaterally ovariectomized rats were injected with cocaine (10 mg kg-1 day-1) or with saline for 2 weeks. Each rat received estradiol benzoate (50 mg kg-1 day-1 s.c.) for 2 days before sacrifice. Hypothalamic slices were prepared, placed in 0.1 ml microchambers and perfused with modified Krebs buffer (pH 7.4) using a programmable perfusion system. Basal release of norepinephrine (NE) and serotonin (5HT) was significantly increased in the cocaine-treated group versus controls. Ten-minute pulses of 10(-7)M progesterone (P4) increase NE and 5HT, but not dopamine (DA), release in the saline-treated group. In contrast, pulses of P4 increased NE, but not 5HT or DA, in the cocaine-treated rats. Ten-minute pulses of 0.1 microM NE increased GnRH release in both saline- and cocaine-treated rats. However, the response to pulsed NE was significantly attenuated in the cocaine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)
King
T S
TS
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio.
Schenken
R S
RS
Kang
I S
IS
Javors
M A
MA
Riehl
R M
RM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003042:Cocaine / Q000031:analogs & derivatives / Q000097:blood / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D004971:Estrus / Q000187:drug effects*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007031:Hypothalamus / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D009490:Neurosecretory Systems / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects*; D010906:Pituitary Hormone-Releasing Hormones / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism
D010906:Pituitary Hormone-Releasing Hormones; D012701:Serotonin; C005618:benzoylecgonine; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D003042:Cocaine; D004298:Dopamine; D009638:Norepinephrine