Prenatal cocaine exposure increases anxiety, impairs cognitive function and increases dendritic spine density in adult rats: influence of sex.

Cocaine exposure during pregnancy can impact brain development and have long-term behavioral consequences. The present study examined the lasting consequences of prenatal cocaine (PN-COC) exposure on the performance of cognitive tasks and dendritic spine density in adult male and female rats. From gestational day 8 to 20, dams were treated daily with 30 mg/kg (ip) of cocaine HCl or saline. At 62 days of age, offspring were tested consecutively for anxiety, locomotion, visual memory and spatial memory. PN-COC exposure significantly increased anxiety in both sexes. Object recognition (OR) and placement (OP) tasks were used to assess cognitive function. Behavioral tests consisted of an exploration trial (T1) and a recognition trial (T2) that were separated by an inter-trial delay of varying lengths. Male PN-COC subjects displayed significantly less time investigating new objects or object locations during T2 in both OR and OP tasks. By contrast, female PN-COC subjects exhibited impairments only in OR and only at the longest inter-trial delay interval. In addition, gestational cocaine increased dendritic spine density in the prefrontal cortex and nucleus accumbens in both genders, but only females had increased spine density in the CA1 region of the hippocampus. These data reveal that in-utero exposure to cocaine results in enduring alterations in anxiety, cognitive function and spine density in adulthood. Moreover, cognitive deficits were more profound in males than in females.