Prenatal cocaine eliminates the sex-dependent differences in activation observed in adult rats after cocaine challenge.

In the adult rat, acute administration of cocaine results in enhanced expression of certain behaviors. This activation is often referred to as "stereotypy" because of its repetitive nature. Repeated exposure to the same dose of cocaine does not result in tolerance or a dimunition of these behavioral responses. Rather, an increased responsiveness to cocaine, termed "sensitization," is observed. Female rats, in comparison to male rats, display greater activation to a given dose of cocaine and greater sensitization with repeated exposure. As prenatal cocaine exposure can involve repeated exposure to the drug, we examined the behavioral activation induced by an acute dose of cocaine. Young adult rats of both sexes received a challenge dose of cocaine to determine the long-term effects of repeated in utero exposure to cocaine (30 mg/kg daily, SC) given between gestational days 8-20. As expected, female offspring of dams exposed to saline in utero displayed greater activation to a 20 mg/kg SC dosage of cocaine than their male counterparts. However, these sex differences were completely eliminated by prenatal exposure to cocaine. That is, female rats receiving cocaine during the prenatal period showed no more activation to an acute dose of cocaine as young adults than either control males or those males receiving cocaine in utero. Males exposed in utero to cocaine showed activation to cocaine challenge equivalent to that displayed by males exposed to saline in utero. Prenatal exposure to cocaine may alter sexual differentiation of the brain.

Duke Scholars

Author Frederic J. Seidler Pharmacology & Cancer Biology