Abstract

Dr. Jane Taylor is a leading expert in studying the neural mechanisms underlying addiction vulnerability. She has novel findings from her current SCOR studies indicating increased vulnerability of females to addictive properties of drugs, specifically in the motivation to self-administer drugs such as cocaine. Her group has also shown that early life stress enhances cocaine self administration, while related SCOR research has shown that such effects occur in a sex-specific manner, with stressed females being more vulnerable to addictive behaviors than non-stressed females. Molecular and cellular mechanisms underlying this sex-specific vulnerability are not well understood. The proposed basic science project builds on this research and will specifically examine the effects of sex-specific factors (e.g. sex hormones and sex chromosome) on CRF/chronic stress interactions with dopamine signaling in the critical reward regions such as the ventral tegmental area (VTA). The effects of these factors will be assessed in each stage of the cocaine use cycle, namely, drug acquisition, binge and reinstatement in order to fully identify sex, stress and cocaine effects in each of these stages in both female and male animals (including rodents and transgenic lines of mice). These studies will be the first to comprehensively examine the effects of sex factors, stress mechanisms and cocaine effects in reward circuits. We expect the findings from these studies to directly inform clinical research by identifying markers that could be used to predict vulnerability both to develop cocaine dependence and to relapse in women. The studies will more broadly identify potential mechanisms underlying sex differences in vulnerability to develop SUDs. Together, a greater understanding of the molecular and neurochemical differences underlying cocaine dependence in men and women will identify molecular targets that may be used to develop gender-specific prevention and treatment strategies in SUDs.

Steiner RC, Hsiung HM, Picciotto MR (2006) Cocaine self-administration and locomotor sensitization are not altered in CART knockout mice. Behav Brain Res. 171(1):56-62.

Lynch WJ, Mangini L and Taylor JR (2005). Neonatal isolation stress potentiates cocaine seeking behavior in adult male and female rats.  Neuropsychopharmacology, 30(2):322-9.

Lynch WJ and Taylor JR (2005a). Decreased motivation following cocaine self-administration under extended access conditions: Effects of sex and oviarian hormones. Neuropsychopharmacology, 30(5) 927-35.

Lynch WJ and Taylor JR (2005b). Persistent changes in motivation to self-administer cocaine following modulation of cyclic AMP-dependent protein kinase A (PKA) activity in the nucleus accumbens. EurJ Neurosci, 22:1214-1220.

Lynch WJ and Taylor JR (2004) Sex differences in the behavioral effects of 24-hr/day access to cocaine under a discrete trial procedure. Neuropsychopharmacology, 29(5):943-51.

Carruth LL, Reisert I, Arnold AP (2002) Sex chromosome genes directly affect brain sexual differentiation. Nat Neurosci. 5(10):933-4.

Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko, Koob GF, Vale WW, Lee K-F (2000) Mice deficient for corticotrophin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nature 24:410-414.

Bale TL and Vale, WW (2004) CRF and CRF receptors: role of stress responsivity and other behaviors. Ann. Rev. Pharmacol. Toxicol, 44: 525-57.

Jentsch JD and Taylor JR (2003) Sex-related differences in spatial divided attention and motor impulsivity in rats. Behavioral Neuroscience, 117(1):76-83.

Bale TL, Picetti R, Contarino A, Koob, GF, Vale, WW, and Kuo-Fen L (2002). Mice deficient for both corticotrophin-releasing factor receptor 1 (CRFR1) and CRFR2 have an impaired stress response and display sexually dichotomous anxiety-like behavior.  J Neurosci., 22(1): 193-199.

Unpublished Article

Lynch WJ, Kiraly, DD, Caldarone BJ, Picciotto MR, and Taylor JR Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats (2006). Psychopharmacology, under review

Recent Abstracts

Krueger DD, Olausson P, Wu T, Williams KR, Taylor JR and Nairn AC (2005) Proteomic analysis of persistent cortico-limbic-striatal neuroadaptations following repeated cocaine exposure in Vervet monkeys.  Program # 1030.6, 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. Online.

Quinn JJ, Sanchez H, Taylor JR.  (2005).  Corticotropin-releasing hormone in the ventral tegmental area modulates cocaine-induced locomotor sensitization. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. Online.

Quinn JJ, Hitchcott PK, Arnold AP, Taylor JR.  (2006).  Chromosomal sex determines habit formation: Relevance to addiction. 2006 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. Online.

Quinn JJ, Hitchcott PK, Pesquera FR, Arnold AP, Taylor JR.  (2006b).  Sex differences in habit formation and sensitization to cocaine: Independent contributions of chromosomal sex and gonadal sex.  Third Annual Interdisciplinary Women’s Health Research Symposium, National Institutes of Health.

Wiseman, J.L., Lynch, W.J., Olausson P., Taylor, J.R. (2005) Sex differences in reward-related learning after repeated nicotine exposure during adolescence. 2005 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience. Online.

Sanchez H, Quinn JJ, Taylor JR (2006)Sex differences in contextual fear conditioning: A role for dorsal hippocampus 17-b-estradiol. Soc for Neurosci Abstracts.