Over the past five years, the applicant has developed a research and mentoring program that is central to clinical drug abuse research at UCLA. He is P.I. on a training grant (T32 MH19200), which supports 2 predoctoral students and 3 postdoctoral trainees. He has also developed a clinical research education program (R25 DA14593) to provide additional training in clinical research for clinically trained physicians or psychologists. These training programs complement two other institutional training grants on which he participates, the Psychobiology Training Program, T32 MH017140 (Dr. Andrew Leuchter, P.I.), and the Drug Abuse Training Program, T32 DA007272 (Dr. Richard Rawson, P.I.). These programs specifically complement the mentoring component of the proposed Midcareer Investigator Award in Patient-oriented Research. The applicant's research program has emphasized study of neurobiological changes associated with methamphetamine dependence. In addition, he has developed a human laboratory program that uses information regarding these neurobiological changes in order to inform the development of medication treatments for stimulant dependence. He proposes to expand this research program to include studies of neuroimmune effects of stress in order to characterize factors important in stimulant dependence more fully. """"""""Stress"""""""" is hypothesized to contribute to relapse in individuals with substance dependence and this has been studied using preclinical animal models, exemplified by the reinstatement model of relapse. In the reinstatement model, extinguished drug-seeking behavior is reinstated by exposure to a stressor or by administration of a """"""""priming"""""""" dose of the previously self-administered drug. The applicant proposes to examine the effects of exposure to an experimental stressor and of administration of a priming dose of methamphetamine on neuroimmune measures, drug craving, and on drug seeking behavior in methamphetamine dependent volunteers. The role played by changes in neuroimmune measures following exposure to stress or methamphetamine in mediating the development of craving and drug-seeking behavior will then be examined. A more complete understanding of stress-related aspects of addiction will facilitate the development of treatments for stimulant dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DA017754-02
Application #
7107314
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Czechowicz, Dorynne D
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$124,200
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Mahoney 3rd, James J; Newton, Thomas F; Omar, Yasmine et al. (2013) The relationship between lifetime stress and addiction severity in cocaine-dependent participants. Eur Neuropsychopharmacol 23:351-7
Mahoney, James J; Jackson, Brian J; Kalechstein, Ari D et al. (2012) Acute modafinil exposure reduces daytime sleepiness in abstinent methamphetamine-dependent volunteers. Int J Neuropsychopharmacol 15:1241-9
Haile, Colin N; De La Garza 2nd, Richard; Mahoney 3rd, James J et al. (2012) The impact of disulfiram treatment on the reinforcing effects of cocaine: a randomized clinical trial. PLoS One 7:e47702
Newton, Thomas F; De La Garza 2nd, Richard; Brown, Gregory et al. (2012) Noradrenergic ?? receptor antagonist treatment attenuates positive subjective effects of cocaine in humans: a randomized trial. PLoS One 7:e30854
Mahoney 3rd, James J; Jackson, Brian J; Kalechstein, Ari D et al. (2011) Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline. Prog Neuropsychopharmacol Biol Psychiatry 35:459-65
Kalechstein, Ari D; De La Garza 2nd, Richard; Newton, Thomas F (2010) Modafinil administration improves working memory in methamphetamine-dependent individuals who demonstrate baseline impairment. Am J Addict 19:340-4
Haile, Colin N; De La Garza 2nd, Richard; Newton, Thomas F (2010) Methamphetamine Cured my Cocaine Addiction. J Addict Res Ther 1:
De La Garza 2nd, Richard; Zorick, Todd; London, Edythe D et al. (2010) Evaluation of modafinil effects on cardiovascular, subjective, and reinforcing effects of methamphetamine in methamphetamine-dependent volunteers. Drug Alcohol Depend 106:173-80
Culbertson, Christopher; Nicolas, Sam; Zaharovits, Itay et al. (2010) Methamphetamine craving induced in an online virtual reality environment. Pharmacol Biochem Behav 96:454-60

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