Abstract

Adolescence is a critical period in the maturation of a subcortical-prefrontal neural systems central to stress regulation and the regulation of rewarding behaviors underlying SUDs.  Emerging preclinical and clinical data identify prenatal cocaine and other drug exposure (PCE) and early life stress as major vulnerability factors associated with dysregulated stress responses adolescence and young adulthood and those associated with risk of SUDs. Evidence from SCOR-supported research indicates that early trauma increases susceptibility to abuse substances in girls but not boys, a vulnerability factor that continues to affect course of addiction and relapse. Other evidence indicates that PCE is associated with increased aggression and behavior problems that is moderated by gender, and that such behaviors predict onset of SUDs. No previous research has examined the separate and synergistic effects of these factors on onset of SUDs in a prospective group of children at risk of developing SUDs. This project will assess sex differences in the effects of PCE and early trauma on stress responses and vulnerability to engage in substance use behaviors. The study will involve a cohort of well-characterized adolescent males and females beginning at age 14 who have been studied since birth and who will participate in laboratory based stress-induction sessions with detailed assessments of their behavioral and physiological response. They will be prospectively followed with bi-yearly assessments of drug use behaviors. This will be the first study in humans to examine sex-specific effects of PCE on stress and it’s subsequent effect on drug use behaviors. Such data increase our understanding of the mechanisms underlying increased risk of SUDs in girls, and lead to the development of more effective and targeted interventions in at-risk adolescent girls.

Relevant Previous Publications (In Print)

Mayes, L.C., Bornstein, M.H., Chawarska, K., and Granger, R.H. (1996). Impaired regulation of arousal in 3-month-old infants exposed prenatally to cocaine and other drugs.  Development and Psychopathology, 8: 29-42.

Sinha R, Catapano D, O'Malley SS (1999). Stress-induced craving and stress responses in cocaine dependent individuals. Psychopharmacology, 142: 343-351.

Fox HC, Garcia M, Kemp K, Milivojevic V, Kreek MJ, and Sinha R (2006). Gender differences in cardiovascular and corticoadrenal response to stress and drug cues in cocaine dependent individuals. Psychopharmacology, 185: 348-357.

Mayes L.C. (2002).  A behavioral teratogenic model of the impact of prenatal Cocaine exposure on arousal regulatory systems.   Neurotoxicology and Teratology. 12: 384-396.

Sinha R, Talih M, Malison, R, Anderson GA, Cooney N, Kreek MJ (2003). Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology, 170: 62-72.

Mayes, L.C., Cicchetti, D., Acharyya, S.,  Zhang, H. (2003). Developmental
Trajectories of Cocaine-and-Other-Drug-Exposed and Non-Cocaine-Exposed Children. Journal of Developmental & Behavioral Pediatrics. 24: 323-335.

Molitor, A., Mayes, L.C., Ward, A. (2003) Emotion regulation behavior during a separation procedure in 18-month-old children of mothers using cocaine and other drugs.  Development and Psychopathology, 15: 39-54.

Schroder, M., Snyder, P., Sielski, I. & Mayes, L.C. (2004).  Impaired performance of children exposed in-utero to cocaine on a novel test of visuospatial working memory. Brain and Cognition. 55 (2): 409-12.

Mayes, L.C., Molfese, D.L., Key, A.F. , & Hunter, N. (2005).  Event-Related Potentials In Cocaine-Exposed Children During A Stroop Task.  Neurotoxicology and Teratology. 27: 797-813.

Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ (2006). Stress-induced cocaine craving and hypothalamic-pituitary-adrenal responses are predictive of cocaine relapse outcomes. Archives of General Psychiatry, 63: 324-331.