COCAINE LETHALITY INCREASES DURING LATE-GESTATION IN THE RAT - A STUDY OF CRITICAL PERIODS OF EXPOSURE

OBJECTIVE: Cocaine-associated morbidities in pregnant women (e.g., abr uptio placentae, hypertension, seizures) occur mostly during the final stages of gestation. The purpose of our study was to determine whethe r cocaine's toxicity and blood levels Varied as a function of ''critic al periods'' of exposure during gestation. STUDY DESIGN: To evaluate m ortality rates, pregnant Long-Evans rats received subcutaneously 30, 4 0, or 50 mg/kg cocaine hydrochloride twice daily (C30, C40, and C50 gr oups) either during gestational days 7 to 13 (midgestation) or gestati onal days 14 to 20 (late gestation) (n = 9 to 20 per group). Serum lev els of the cocaine metabolite benzoylecgonine were examined in other g roups of rats on either gestational day 13 (mid) or day 20 (late) in t he C30 treatment condition (n = 5 and 10 per group). RESULTS: There we re no maternal mortalities in the midgestation groups at any dose. In contrast, the late-gestation groups showed a dramatic dose-dependent e ffect, with maternal mortality rates of 0%, 40%, and 72% in the C30, C 40, and G50 groups. The late-gestation group had higher benzoylecgonin e levels than the midgestation groups did. CONCLUSIONS: Late gestation was associated with higher maternal mortality rates and higher benzoy lecgonine levels, indicating that some underlying physiologic change e nhanced cocaine's toxicity as pregnancy progressed. This increased sen sitivity to cocaine may be mediated by estrogen or progesterone, sugge sting that the cocaine-abusing woman is at increased risk for cocaine- induced morbidities whenever levels of these hormones are elevated, su ch as during the final stages of pregnancy or possibly when taking ora l contraceptives.