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OPIOD - DOPAMINE INTERACTIONS IN COCAINE ABUSE

Award Number: K01DA000414
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/01/2000
PERIOD OF PERFORMANCE END DATE: 01/31/2005

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OPIOD - DOPAMINE INTERACTIONS IN COCAINE ABUSE - This is a request for a Mentored Research Scientist Development Award (KO1). The proposed research is designed to elucidate the relationship between the opioid system and the dopamine system as a result of exposure to cocaine. The majority of what we know of cocaine's effects on the endogenous opioid system has been based on investigations carried out in rats. These studies may be of limited relevance however, to cocaine abuse in humans, because of the differences in expression of opioid receptors in rat vs human brain, as well as, neuroanatomical and neurochemical differences between these species. Moreover, the effects of self-administration on opioid receptors are largely unknown. A strategy combining in vivo and in vitro imaging methods is proposed to assess neuroadaptations in opioid and dopamine receptors that accompany cocaine self-administration in a primate model of cocaine abuse. The primary focus of the proposed studies is training in positron emission tomography (PET) imaging to map changes in brain receptor function that occur over time as a consequence of cocaine self-administration and in response to a buprenorphine treatment regimen. One of the strengths of PET is that these parameters can be evaluated longitudinally within the same subjects thereby reducing error that is inherent in a between animal study. The data obtained with PET will be directly compared to data analyzed using in vitro autoradiographic techniques in the same subjects analyzed with PET as well as in groups of animals treated under identical conditions. Because alterations in receptor KD and BMAX values do not always correlate with functional activation of those receptors, the effects of these treatments on functional activation of opioid receptors will also be assessed with the [35S]GTPgammaS autoradiographic method which is used to identify receptor-activated G-proteins. A major strength of this proposal is the utilization of different experimental approaches that complement each other to assess the functional and anatomical distribution of receptors. The multidisciplined nature of this project, which will be conducted under the mentorship of Dr. Robert Mach, and in collaboration with faculty specializing in primate behavior, opioid/cocaine pharmacology and signal transduction, will provide a unique opportunity for the candidate to address issues regarding the long-term effects of cocaine. This project will thus enable the candidate to develop into an independent investigator in the sparsely populated arena of primate neurobiology to investigate the neurobiological substrates underlying the long-term effects of cocaine abuse.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2004 ( Subtotal = $98,269 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Abuse Scientist Development Awards, Research Scientist Development Awards, and Research Scientist Awards	000	5	1/20/2004	NON-COMPETING CONTINUATION	$98,269
														Subtotal = $98,269

Issue Date FY: 2003 ( Subtotal = $106,947 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Abuse Scientist Development Awards, Research Scientist Development Awards, and Research Scientist Awards	000	4		NON-COMPETING CONTINUATION	$106,947
														Subtotal = $106,947

Issue Date FY: 2002 ( Subtotal = $117,934 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Abuse Scientist Development Awards, Research Scientist Development Awards, and Research Scientist Awards	000	3	1/24/2002	NON-COMPETING CONTINUATION	$117,934
														Subtotal = $117,934

Issue Date FY: 2001 ( Subtotal = $115,978 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Abuse Scientist Development Awards, Research Scientist Development Awards, and Research Scientist Awards	000	2	1/26/2001	NON-COMPETING CONTINUATION	$115,978
														Subtotal = $115,978

Issue Date FY: 2000 ( Subtotal = $112,600 )
2000	2000	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Abuse Scientist Development Awards, Research Scientist Development Awards, and Research Scientist Awards	000	1	1/19/2000	NEW	$112,600
														Subtotal = $112,600

Grand Total All Awards = $551,728

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OPIOD - DOPAMINE INTERACTIONS IN COCAINE ABUSE

Award Number: K01DA000414

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/01/2000

PERIOD OF PERFORMANCE END DATE: 01/31/2005

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