This KO2 application seeks support which is essential for my continued career development as a newly-independent clinical researcher. Funded by a NIDA institutional training grant, I have attained considerable expertise in the brain imaging of psychostimulant addiction over the past 4 years. I have demonstrated considerable research productivity as evidenced by my peer-reviewed publications, my scientific co-directorship of a major center, my principal- and co-investigatorships on two center sections, and a recently-awarded ROI. However this source of salary support (75%) will expire 6/31/98, leading me to seek an alternative mechanism of funding. Therefore, this KO2 award is vital for sustaining my current full- time research focus and for facilitating my maturation into a fully-independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan which fills important gaps in my current expertise in SPECT/PET neuroreceptor methods. Specifically, I will acquire specialized skills in several additional multidisciplinary areas: l) authorized use of radioisotopes in humans, 2) mathematical modeling and neuroreceptor quantitation, 3) digital processing and statistical analysis of imaging data, and 4) basic neurobiology of abused drugs. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings. Two representative, funded research studies are included which test two major neurochemical hypotheses of cocaine dependence in humans: sensitization and dopamine (DA) deficiency. Study #1: To establish whether cocaine addicts show a sensitized response to amphetamine as evidenced by increased displacement of the D2 radiotracer [123I]IBZM. Study #2: To determine whether cocaine addicts have reduced basal levels of DA as evidenced by smaller increases in [123I]IBZM binding following DA depletion by alpha-methyl.para-tyrosine (AMPT). These investigations illustrate the considerable impact this career award will have in furthering not only my scientific career, and also our fundamental understanding of the neurochemical mechanisms and adaptations which accompany cocaine addiction.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Development Award - Research (K02)
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Special Emphasis Panel (ZDA1-MXS-M (09))
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Yale University
Schools of Medicine
New Haven
United States
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Angarita, Gustavo A; Pittman, Brian; Gueorguieva, Ralitza et al. (2010) Regulation of cocaine self-administration in humans: lack of evidence for loading and maintenance phases. Pharmacol Biochem Behav 95:51-5
Morgan, Peter T; Pace-Schott, Edward F; Sahul, Zakir H et al. (2008) Sleep architecture, cocaine and visual learning. Addiction 103:1344-52
Pace-Schott, Edward F; Morgan, Peter T; Malison, Robert T et al. (2008) Cocaine users differ from normals on cognitive tasks which show poorer performance during drug abstinence. Am J Drug Alcohol Abuse 34:109-21
Morgan, Peter T; Malison, Robert T (2007) Cocaine and sleep: early abstinence. ScientificWorldJournal 7:223-30
Morgan, Peter T; Pace-Schott, Edward F; Sahul, Zakir H et al. (2006) Sleep, sleep-dependent procedural learning and vigilance in chronic cocaine users: Evidence for occult insomnia. Drug Alcohol Depend 82:238-49
Malison, Robert T; Kranzler, Henry R; Yang, Bao-Zhu et al. (2006) Human clock, PER1 and PER2 polymorphisms: lack of association with cocaine dependence susceptibility and cocaine-induced paranoia. Psychiatr Genet 16:245-9
Fox, Helen C; Talih, Makram; Malison, Robert et al. (2005) Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues. Psychoneuroendocrinology 30:880-91
Sinha, Rajita; Talih, Makram; Malison, Robert et al. (2003) Hypothalamic-pituitary-adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology (Berl) 170:62-72