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NEUROBIOLOGY OF SPEEDBALL SELF-ADMINISTRATION

Award Number: R01DA012498
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/20/2000
PERIOD OF PERFORMANCE END DATE: 11/30/2013

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NEUROBIOLOGY OF SPEEDBALL SELF-ADMINISTRATION - Intravenous drug use continues to be a major public health problem which is a significant vector for the spread of AIDS with the co-use of cocaine and opiate agonists increasing and recentlyshown to decrease the likelihood of a successful treatment outcome. This application proposes the continuation of research into the mechanisms underlying the self-administration of cocaine and heroin and the potentiation of the neurochemical effects of cocaine by heroin. During this last funding period, heroin was shown to potentiate the effects of cocaine on the increase in nucleus accumbens extracellular fluid levels of dopamine at self- administered doses on the ascending limb of the dose-intake relationship. It was also found that the effect of the combination of these two drugs on self-administration was both additive in an isobolographic analysis and synergistic in a choice procedure. In addition, it was shown that ventral pallidal and ventral tegmental area u opioid receptors are important in the effects upon self-administration since alkylation of these receptors shifted dose-intake relationships to that of cocaine alone. Experiments are proposed to define the role of glutamate (Glu) and v-aminobutyric acid (GABA) neurons in the medial prefrontal cortex, nucleus accumbens, ventral pallidum and ventral tegmental area in the effects upon self-administration and upon the neurochemical potentiation. This involvement of Glu and GABA releasing neurons will beassessed with microdialysis techniques, laser capture microdissection, gene expression profiling and protein measurements of discrete neuronal subgroups to characterizethe neuro-adaptations that occur in response to the self-administration of cocaine/heroin combinations. These data will be used to expand upon a model of opiate-stimulant interactions that will be further tested through the use of intracerebral injections of specific GABA and Glu receptor agonists and antagonists to identify and verify the participation of neurons containing the critical opiate receptors responsible for the effects upon self-administration of the combination and the neurochemical potentiation of cocaine by heroin. Relevance: The concurrent use of COC and opiate combinations has increased since the 1970's and now represents a significant subset of intravenous drug abusers. This co-abuse has negative consequences since a high level of COC use at intake has been reported to decreasethe likelihood of a positive treatment outcome for opiate addicts. This application proposes the continuation of research into the mechanisms underlying the self-administration of cocaine and heroin combinations and the potentiation of the neurochemical effects of cocaine by heroin demonstrated in this last funding period. Clearly, knowledge of the mechanisms of this enhancement could be helpful in the development of therapeutic strategies to treat this co-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: 2013 ( Subtotal = $0 )
2013	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	10	11/27/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2012 ( Subtotal = $0 )
2012	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	10	1/10/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $246,205 )
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	10	1/21/2011	NON-COMPETING CONTINUATION	$228,438
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	10	6/6/2011	NON-COMPETING CONTINUATION	$17,767
														Subtotal = $246,205

Issue Date FY: 2010 ( Subtotal = $251,282 )
2010	2010	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	9	1/13/2010	NON-COMPETING CONTINUATION	$251,282
														Subtotal = $251,282

Issue Date FY: 2009 ( Subtotal = $253,820 )
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	8	12/2/2008	NON-COMPETING CONTINUATION	$228,438
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	8	4/27/2009	NON-COMPETING CONTINUATION	$25,382
														Subtotal = $253,820

Issue Date FY: 2008 ( Subtotal = $253,820 )
2008	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	7	11/29/2007	NON-COMPETING CONTINUATION	$253,820
														Subtotal = $253,820

Issue Date FY: 2007 ( Subtotal = $258,708 )
2007	2007	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	6	4/30/2007	COMPETING CONTINUATION	$258,708
														Subtotal = $258,708

Issue Date FY: 2004 ( Subtotal = $245,389 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	5	2/2/2004	NON-COMPETING CONTINUATION	$245,389
														Subtotal = $245,389

Issue Date FY: 2003 ( Subtotal = $238,332 )
2003	2003	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Use and Addiction Research Programs	000	4		NON-COMPETING CONTINUATION	$238,332
														Subtotal = $238,332

Issue Date FY: 2002 ( Subtotal = $231,815 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Use and Addiction Research Programs	000	3	1/23/2002	NON-COMPETING CONTINUATION	$231,815
														Subtotal = $231,815

Issue Date FY: 2001 ( Subtotal = $225,931 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Use and Addiction Research Programs	000	2	2/9/2001	NON-COMPETING CONTINUATION	$225,931
														Subtotal = $225,931

Issue Date FY: 2000 ( Subtotal = $243,026 )
2000	2000	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Use and Addiction Research Programs	000	1	9/21/2000	NEW	$243,026
														Subtotal = $243,026

Grand Total All Awards = $2,448,328

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NEUROBIOLOGY OF SPEEDBALL SELF-ADMINISTRATION

Award Number: R01DA012498

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/20/2000

PERIOD OF PERFORMANCE END DATE: 11/30/2013

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