Cocaine's lethality increases during late gestation in the rat: a study of "critical periods" of exposure.
OBJECTIVE
Cocaine-associated morbidities in pregnant women (e.g., abruptio placentae, hypertension, seizures) occur mostly during the final stages of gestation. The purpose of our study was to determine whether cocaine's toxicity and blood levels varied as a function of "critical periods" of exposure during gestation.


METHODS
To evaluate mortality rates, pregnant Long-Evans rats received subcutaneously 30, 40, or 50 mg/kg cocaine hydrochloride twice daily (C30, C40, and C50 groups) either during gestational days 7 to 13 (midgestation) or gestational days 14 to 20 (late gestation) (n 9 to 20 per group). Serum levels of the cocaine metabolite benzoylecgonine were examined in other groups of rats on either gestational day 13 (mid) or day 20 (late) in the C30 treatment condition (n = 5 and 10 per group).


RESULTS
There were no maternal mortalities in the midgestation groups at any dose. In contrast, the late-gestation groups showed a dramatic dose-dependent effect, with maternal mortality rates of 0%, 40%, and 72% in the C30, C40, and C50 groups. The late-gestation group had higher benzoylecgonine levels than the midgestation groups did.


CONCLUSIONS
Late gestation was associated with higher maternal mortality rates and higher benzoylecgonine levels, indicating that some underlying physiologic change enhanced cocaine's toxicity as pregnancy progressed. This increased sensitivity to cocaine may be mediated by estrogen or progesterone, suggesting that the cocaine-abusing woman is at increased risk for cocaine-induced morbidities whenever levels of these hormones are elevated, such as during the final stages of pregnancy or possibly when taking oral contraceptives.
Church
M W
MW
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Subramanian
M G
MG
D000818:Animals; D003042:Cocaine / Q000031:analogs & derivatives / Q000097:blood / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D009026:Mortality; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood / Q000187:drug effects*; D051381:Rats
C005618:benzoylecgonine; D003042:Cocaine