Chronic cocaine disruption of estrous cyclicity in the rat: Dose-dependent effects

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Abstract

The effects of cocaine on cyclic reproductive function in females remain largely unknown. In this study, we sought to define the range of doses of cocaine effective in disrupting estrous cyclicity and inhibiting ovulation. Estrous cyclicity was monitored daily by vaginal cytology. Group 1 consisted of rats receiving no treatment. Group 2 consisted of rats injected daily with saline s.c. Groups 3 to 6 consisted of rats injected with 1, 5, 10 and 20 mg/kg/day of cocaine HCl s.c., respectively. Group 7 consisted of rats that were food-restricted to allow weight gains comparable to those of group 6. Our results indicate a dose- dependent effect of cocaine on estrous cyclicity with an estimated IC50 of 8.5 mg/kg/day (i.e., the dose of cocaine required to inhibit the number of proestrus:estrus events per 3- week period of analysis by 50%). Over 50% of the rats with cycle disruption on 10 mg/kg/day of cocaine, but almost none of those with cycle disruption on 20 mg/kg/day, returned to normal cyclic patterns after cessation of cocaine treatment. Serum luteinizing hormone levels were reduced 53 and 74% by 10 and 20 mg/kg/day of cocaine, respectively, with an IC50 of 8.9 mg/kg/day. In contrast, cocaine had no significant effect at any of the tested dosages on serum follicle-stimulating hormone or prolactin levels. Ovulation rates were significantly reduced at both 10 and 20 mg/kg/day of cocaine (IC50 = 11 mg/kg/day of cocaine). These data demonstrate that the effects of cocaine to disrupt cyclic reproductive function, including circulating gonadotropin levels, estrous cyclicity and rates of ovulation in rats, is dose dependent and, at higher doses, may be irreversible in some animals.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume264
Issue number1
StatePublished - 1993

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Periodicity
Cocaine
Ovulation
Inhibitory Concentration 50
Proestrus
Withholding Treatment
Estrus
Follicle Stimulating Hormone
Luteinizing Hormone
Serum
Gonadotropins
Prolactin
Weight Gain
Cell Biology
Demography
Food

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Chronic cocaine disruption of estrous cyclicity in the rat: Dose-dependent effects",
abstract = "The effects of cocaine on cyclic reproductive function in females remain largely unknown. In this study, we sought to define the range of doses of cocaine effective in disrupting estrous cyclicity and inhibiting ovulation. Estrous cyclicity was monitored daily by vaginal cytology. Group 1 consisted of rats receiving no treatment. Group 2 consisted of rats injected daily with saline s.c. Groups 3 to 6 consisted of rats injected with 1, 5, 10 and 20 mg/kg/day of cocaine HCl s.c., respectively. Group 7 consisted of rats that were food-restricted to allow weight gains comparable to those of group 6. Our results indicate a dose- dependent effect of cocaine on estrous cyclicity with an estimated IC50 of 8.5 mg/kg/day (i.e., the dose of cocaine required to inhibit the number of proestrus:estrus events per 3- week period of analysis by 50{\%}). Over 50{\%} of the rats with cycle disruption on 10 mg/kg/day of cocaine, but almost none of those with cycle disruption on 20 mg/kg/day, returned to normal cyclic patterns after cessation of cocaine treatment. Serum luteinizing hormone levels were reduced 53 and 74{\%} by 10 and 20 mg/kg/day of cocaine, respectively, with an IC50 of 8.9 mg/kg/day. In contrast, cocaine had no significant effect at any of the tested dosages on serum follicle-stimulating hormone or prolactin levels. Ovulation rates were significantly reduced at both 10 and 20 mg/kg/day of cocaine (IC50 = 11 mg/kg/day of cocaine). These data demonstrate that the effects of cocaine to disrupt cyclic reproductive function, including circulating gonadotropin levels, estrous cyclicity and rates of ovulation in rats, is dose dependent and, at higher doses, may be irreversible in some animals.",
author = "King, {Thomas S} and Canez, {M. S.} and S. Gaskill and Javors, {Martin A} and Schenken, {Robert S}",
year = "1993",
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T1 - Chronic cocaine disruption of estrous cyclicity in the rat

T2 - Dose-dependent effects

AU - King, Thomas S

AU - Canez, M. S.

AU - Gaskill, S.

AU - Javors, Martin A

AU - Schenken, Robert S

PY - 1993

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N2 - The effects of cocaine on cyclic reproductive function in females remain largely unknown. In this study, we sought to define the range of doses of cocaine effective in disrupting estrous cyclicity and inhibiting ovulation. Estrous cyclicity was monitored daily by vaginal cytology. Group 1 consisted of rats receiving no treatment. Group 2 consisted of rats injected daily with saline s.c. Groups 3 to 6 consisted of rats injected with 1, 5, 10 and 20 mg/kg/day of cocaine HCl s.c., respectively. Group 7 consisted of rats that were food-restricted to allow weight gains comparable to those of group 6. Our results indicate a dose- dependent effect of cocaine on estrous cyclicity with an estimated IC50 of 8.5 mg/kg/day (i.e., the dose of cocaine required to inhibit the number of proestrus:estrus events per 3- week period of analysis by 50%). Over 50% of the rats with cycle disruption on 10 mg/kg/day of cocaine, but almost none of those with cycle disruption on 20 mg/kg/day, returned to normal cyclic patterns after cessation of cocaine treatment. Serum luteinizing hormone levels were reduced 53 and 74% by 10 and 20 mg/kg/day of cocaine, respectively, with an IC50 of 8.9 mg/kg/day. In contrast, cocaine had no significant effect at any of the tested dosages on serum follicle-stimulating hormone or prolactin levels. Ovulation rates were significantly reduced at both 10 and 20 mg/kg/day of cocaine (IC50 = 11 mg/kg/day of cocaine). These data demonstrate that the effects of cocaine to disrupt cyclic reproductive function, including circulating gonadotropin levels, estrous cyclicity and rates of ovulation in rats, is dose dependent and, at higher doses, may be irreversible in some animals.

AB - The effects of cocaine on cyclic reproductive function in females remain largely unknown. In this study, we sought to define the range of doses of cocaine effective in disrupting estrous cyclicity and inhibiting ovulation. Estrous cyclicity was monitored daily by vaginal cytology. Group 1 consisted of rats receiving no treatment. Group 2 consisted of rats injected daily with saline s.c. Groups 3 to 6 consisted of rats injected with 1, 5, 10 and 20 mg/kg/day of cocaine HCl s.c., respectively. Group 7 consisted of rats that were food-restricted to allow weight gains comparable to those of group 6. Our results indicate a dose- dependent effect of cocaine on estrous cyclicity with an estimated IC50 of 8.5 mg/kg/day (i.e., the dose of cocaine required to inhibit the number of proestrus:estrus events per 3- week period of analysis by 50%). Over 50% of the rats with cycle disruption on 10 mg/kg/day of cocaine, but almost none of those with cycle disruption on 20 mg/kg/day, returned to normal cyclic patterns after cessation of cocaine treatment. Serum luteinizing hormone levels were reduced 53 and 74% by 10 and 20 mg/kg/day of cocaine, respectively, with an IC50 of 8.9 mg/kg/day. In contrast, cocaine had no significant effect at any of the tested dosages on serum follicle-stimulating hormone or prolactin levels. Ovulation rates were significantly reduced at both 10 and 20 mg/kg/day of cocaine (IC50 = 11 mg/kg/day of cocaine). These data demonstrate that the effects of cocaine to disrupt cyclic reproductive function, including circulating gonadotropin levels, estrous cyclicity and rates of ovulation in rats, is dose dependent and, at higher doses, may be irreversible in some animals.

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