Prenatal cocaine potentiates the effects of morphine in adult mice

Prenatal cocaine exposure has been reported to result in abnormal neurobehavioral development, both in animals and humans. In this study, outbred CD-1 mice were exposed in utero to cocaine hydrochloride administered daily as i.p. injections to dams from day 10 of gestation to day 16, at the dose 0, 5 or 50 mg/kg. Cocaine did not alter duration of pregnancy while it decreased the difference in maternal body weight from days 10 to 16 in the dams receiving the higher dose of cocaine. The body weight of the offspring from birth to 15 days of age and the physical maturation were not affected by prenatal cocaine exposure. The development of the response to strong tactile stimulation was either slightly delayed in the 5 mg/kg group or markedly accelerated in the 50 mg/kg group. At adulthood, animals were assessed for behavioral responses to a novel environment, for response to painful stimulation (hot-plate test set at 55 ± 1°C), and for the effects of a single morphine injection (30 mg/kg, i.p.). Data showed that in the absence of prenatal cocaine exposure effects, morphine increased the time spent in inactivity, while it decreased rearing, grooming and bar-holding behaviors. In the case of sniffing, morphine increased this behavior, except in the 5 mg/kg cocaine group. Moreover, morphine administration induced the expected increase of locomotion, irrespective of prenatal condition. With respect to pain reactivity, prenatal cocaine exposure resulted in an increase of licking latency in the 5 mg/kg group. Morphine administration before the hot-plate test, induced the expected analgesia, which was particularly evident in mice receiving 5 mg/kg of cocaine. The present results suggest that gestational cocaine exposure is associated with changes in development of sensory response and with an enhancement of the sensitivity to morphine. © 1994.