Prenatal cocaine exposure (PCE) has consistently been associated with behavioral deficits through childhood, adolescence, and young adulthood in our ongoing study. Further, 21-year-olds with PCE in our study were twice as likely to have been arrested as non-exposed offspring, were more likely to be diagnosed with Conduct Disorder, had higher disinhibition scores, were significantly more likely to use alcohol and marijuana earlier, and to have earlier sexual intercourse. The effects of PCE on the developing nervous system may cause changes in brain function that underlie these behavioral outcomes. Previous PCE animal work evaluating changes in tissue/baseline dopamine and its receptor parameters has been mixed and shows relatively small effect sizes. Factors leading to inconsistent findings include differences in: methods used to measure dopamine and its receptor parameters; postnatal age and sex of the animals; and dose and duration of PCE. However, basic investigations that evaluated psychostimulant-induced dopamine release in animals are consistent in reporting increased dopamine transmission compared to controls. In humans, increased striatal dopamine transmission in response to a psychostimulant challenge has been shown to correlate with high impulsivity, novelty, and sensation-seeking traits. Thus, the expression of traits such as delinquency, early sexual intercourse, and substance misuse in PCE may be driven by increased dopamine transmission in the striatum. We will examine this hypothesis in a cohort of young adults in whom PCE was well-documented during pregnancy. [11C]NPA and PET will be used to measure amphetamine-induced dopamine transmission in young adults with PCE and comparison subjects (COMP). We hypothesize that 1a) young adults with PCE will have increased amphetamine-induced dopamine transmission in the striatum relative to COMP and 1b) increased dopamine transmission will be associated with high impulsivity and impaired reward processing behavior. The hypotheses are consistent with the increased dopamine release and firing found in basic PCE investigations. This work has the potential to elucidate the underlying dopaminergic mechanisms that contribute to impulsive and high-risk behaviors in PCE individuals. This is important because an increase in dopamine transmission in the striatum has been linked to traits known to elevate the risk for alcohol and drug use disorders. Understanding the precise mechanisms that contribute to long-term effects of PCE on the brain and expression of high risk behaviors has the potential to inform future therapeutic strategies.
In this study, we will investigate whether the association of prenatal cocaine exposure (PCE) with traits such as delinquency, early sexual intercourse, and substance misuse may be driven by increased dopamine transmission in the striatum. We will use PET imaging to measure amphetamine-induced dopamine transmission in young adults with and without PCE. Understanding the precise mechanisms that contribute to long-term effects of PCE on the brain and expression of high-risk behaviors has the potential to inform future therapeutic strategies.
