This is a competing renewal application for a (K0-5) Senior Scientist Award to continue interdisciplinary research on the neuroendocrine, biologic and behavioral aspects of substance abuse. I am Principal Investigator on three projects: (1) an R01 award to study the neurobiology of nicotine in men and women (DA015067); (2) a NIDA Training Grant to train young scientists in clinical and preclinical research (T32-DA07252); and (3) a NIDA contract for Phase 1 studies of pharmacotherapies for cocaine abuse and dependence (DA38836). I am also Scientific Director of a Program Project (P01-DA14528) to evaluate new strategies for medication-based treatment of cocaine abuse in clinical and preclinical studies. I am a Co-Investigator on four preclinical projects; two R01 awards for preclinical studies of the contribution of gonadal steroid hormones to the reinforcing effects of cocaine (DA14670) and of the interactions between cocaine and mu, kappa and delta opioids (DA02519) and two contracts to assess potential cocaine treatment medications in non human primates (DA7-8073) and in rats (DA0-8806). Several of these clinical and preclinical studies are concerned with the interactions between the neuroendocrine system and the reinforcing effects of cocaine and nicotine. There is increasing evidence that cocaine's abuse liability may be influenced by its stimulation of the hypothalamic-pituitary-adrenal (HPA) axis, and this in turn has suggested new approaches to treatment. The hypothalamic-pituitary-gonadal (HPG) axis is also stimulated by cocaine and preclinical studies suggest that the gonadal steroid hormones may also affect cocaine's behavioral and abuse-related effects under some conditions. We have found striking similarities between the neuroendocrine and behavioral effects of cocaine and nicotine from cigarette smoking, and both are associated with a high degree of morbidity and mortality. The increased vulnerability to infections in cocaine abusers may be associated with suppression of proinflammatory cytokines, which in turn are modulated by changes in adrenal steroid hormones. We hypothesize that interdisciplinary analysis of stimulant drug effects on the interactions between the endocrine system and immune function will clarify a fundamental aspect of the neurobiology of drug abuse and facilitate the discovery of more effective medication-based treatments. My plans for professional growth include continued study of neuroendocrinology as well as immunology. In collaboration with colleagues at the McLean Hospital Brain Imaging Center, I plan to extend our clinical studies of nicotine to explore the temporal correlates between neural activation and localization, and perturbation of the HPA and HPG axis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Award (K05)
Project #
2K05DA000064-27
Application #
6865181
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Wetherington, Cora Lee
Project Start
1979-12-01
Project End
2009-11-30
Budget Start
2004-12-10
Budget End
2005-11-30
Support Year
27
Fiscal Year
2005
Total Cost
$118,584
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Keinan, Eliezer; Abraham, Ayelet Chen; Cohen, Aaron et al. (2018) High-Reynolds Microfluidic Sorting of Large Yeast Populations. Sci Rep 8:13739
Radzinski, Meytal; Fassler, Rosi; Yogev, Ohad et al. (2018) Temporal profiling of redox-dependent heterogeneity in single cells. Elife 7:
Reichmann, Dana; Voth, Wilhelm; Jakob, Ursula (2018) Maintaining a Healthy Proteome during Oxidative Stress. Mol Cell 69:203-213
Mello, Nancy K; Knudson, Inge M; Kelly, Maureen et al. (2011) Effects of progesterone and testosterone on cocaine self-administration and cocaine discrimination by female rhesus monkeys. Neuropsychopharmacology 36:2187-99
Mello, Nancy K (2010) Hormones, nicotine, and cocaine: clinical studies. Horm Behav 58:57-71
Lowen, Steven B; Nickerson, Lisa D; Levin, Jonathan M (2009) Differential effects of acute cocaine and placebo administration on visual cortical activation in healthy subjects measured using BOLD fMRI. Pharmacol Biochem Behav 92:277-82
Goletiani, Nathalie V; Mendelson, Jack H; Sholar, Michelle B et al. (2009) Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men. Pharmacol Biochem Behav 91:526-36
Mello, Nancy K; Negus, S Stevens; Knudson, Inge M et al. (2008) Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys. Neuropsychopharmacology 33:783-95
Mendelson, Jack H; Goletiani, Nathalie; Sholar, Michelle B et al. (2008) Effects of smoking successive low- and high-nicotine cigarettes on hypothalamic-pituitary-adrenal axis hormones and mood in men. Neuropsychopharmacology 33:749-60
Mello, Nancy K; Knudson, Inge M; Mendelson, Jack H (2007) Sex and menstrual cycle effects on progressive ratio measures of cocaine self-administration in cynomolgus monkeys. Neuropsychopharmacology 32:1956-66

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