Abstract

There is now substantial evidence of sex differences in brain structure, chemistry and function (Cahill, 2006; Sinha, 2006c). This research directly affects the development and course of brain disorders such as addiction. In SCOR supported research utilizing functional magnetic resonance imaging (fMRI), we’ve shown that adult men and women activate different neural pathways during stress, circuits that are differentially affected by chronic cocaine abuse in men and women. For example, stress responses in key regions of the corticostriatolimbic pathways involved in the addiction, such as the amygdala, caudate, hippocampus and anterior cingulate cortex, showed gender-specific effects. However, it’s unclear whether these adult men and women show different patterns as a function of chronic cocaine abuse or due to key vulnerability factors, such as prenatal cocaine exposure, that could lead to altered brain responses to stress even prior to chronic cocaine abuse. Therefore, this project will utilize the same cohort of adolescent girls and boys described in Project 2, and assess sex differences in the brain fMRI responses to stress in adolescent girls and boys who have either been exposed or not exposed to prenatal cocaine and other drugs. Whether stress-related neural activity differentially predicts vulnerability to drug use behaviors in girls and boys will also be examined. It will be the first study in the literature to examine the effects of PCE on neural activation associated with stress in at-risk girls and boys. Evidence of sex differences in stress-related neural activation will provide critical information on the developmental differences in neural pathways involved in stress processing and coping in adolescent girls and boys. These data will inform the development of gender-specific prevention strategies to decrease SUD risk.

Relevant Previous Publications (In Print)

Lynch WJ, Potenza MN, Cosgrove KP, Mazure CM. Are women less vulnerable to addiction than men? Under review, Am J Psychiatry

Sinha R (2006). Sex differences in brain fMRI responses to stress. In Canli T (Ed.), Biology of Personality and Individual Differences, Guilford Press, NY, NY, pp. 203-222.

Chambers RA, Taylor JR, Potenza MN (2003) Developmental neurocircuitry of motivation in adolescence: A critical period of addiction vulnerability. Am J Psychiatry 160: 1041-1052.

Mayes LC, Pajulo M (in press) Neurodevelopmental sequelae of prenatal cocaine exposure. In Human Developmental Neurotoxicology. Bellinger D, ed.

Desai RA, Maciejewski PK, Pantalon MV, Potenza MN (2005) Gender differences in adolescent gambling. Ann Clin Psychiatry 17: 249-258.

Potenza MN, Steinberg MA, Skudlarski P, Fulbright RK, Lacadie CM, Wilber MK, Rounsaville BJ, Gore JC, Wexler BE (2003) Gambling urges in pathological gamblers: An fMRI study. Arch Gen Psychiatry 60: 828-836.

Potenza MN, Leung HC, Blumberg HP, Peterson BS, Fulbright RK, Lacadie CM, Skudlarski P, Gore JC (2003) An fMRI Stroop study of ventromedial prefrontal cortical function in pathological gamblers. Am J Psychiatry 160: 1990-1994.

Li C-S, Kosten TR, Sinha, R (2005) Sex differences in brain response to stress imagery in abstinent cocaine dependent individuals - an fMRI study. Biol Psychiatry 57: 487-494.

Li C-S, Kemp K, Milivojevic V, Sinha R (2005). Neuroimaging study of sex differences in the neuropathology of cocaine abuse. Gender Med 2: 174-182.

Sinha R, Lacadie C, Skudlarski P, Fulbright RK, Kosten TR,  Rounsaville BJ, Wexler, BE (2005). Neural activity associated with stress-induced cocaine craving: An fMRI study. Psychopharmacology 183: 171-180.