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Animal Models of Cocaine Addiction

Award Number: R01DA014030
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2011
PERIOD OF PERFORMANCE END DATE: 03/31/2018

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Animal Models of Cocaine Addiction - DESCRIPTION (provided by applicant): The clinical literature has emphasized that the abuse potential of cocaine is related to its speed of onset and that each time a person experiences a rapid and intense cocaine rush there is an increased risk of further drug taking and an increased likelihood of addition. While it is well known that cocaine intake in rats shows a fast- rising loading phase, most rodent models of cocaine addiction instead have focused on the maintenance phase and have explored the effects of long access sessions. The general assumption is that more drug exposure and high intake produces an addicted phenotype. This grant challenges that premise. Our hypothesis is that brief episodes (eg. 5 min) of intense drug use are sufficient to cause a transition from recreational to binge-like patterns of intake. Our data show that self-administration procedures that engender spiking drug levels produce a more robust escalation of drug intake and a dramatic increase in the motivation to self- administer cocaine. Our hypothesis is that the number of 'spikes' (or loading phases) have a much greater impact on the addiction process than the maintenance phase or total drug intake. The experiments proposed in this grant are designed to confirm, extend and validate our initial findings. Specific Aim 1 will test the hypothesis that the number of spikes, the change in spike height and the rise time of each spike is an important determinant of escalation of drug intake and the motivation to response (as measured by a progressive ratio schedule). Specific Aim 1 will also test the hypothesis that cocaine self-administration is regulated by an endogenous circadian influence and that spiking cocaine levels can dysregulate this important physiological control mechanism. Our theoretical viewpoint draws heavily on modeling of cocaine concentrations in brain and it becomes important for us to examine and validate the assumptions underlying the model. Specific Aim 2 will validate the kinetic model using self-administration procedures and will examine the effects of cocaine consumption on extracellular cocaine and dopamine parameters. A method for separating appetitive and consummatory responding will be developed in Specific Aim 3. A two lever procedure will allows us to study cocaine consumption on one lever and the motivation to gain access to cocaine on the other lever. By using a PR schedule and manipulating timeouts and time of day the procedure will enable us to test hypotheses regarding the relationship between brain levels cocaine, drug seeking and drug taking.


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: 2018 ( Subtotal = -$12,283 )
2018	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	13	8/2/2018	NON-COMPETING CONTINUATION	-$12,283
														Subtotal = -$12,283

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	13	4/7/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2015 ( Subtotal = $262,404 )
2015	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	13	4/22/2015	NON-COMPETING CONTINUATION	$262,404
														Subtotal = $262,404

Issue Date FY: 2014 ( Subtotal = $266,400 )
2014	2014	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	12	4/1/2014	NON-COMPETING CONTINUATION	$266,400
														Subtotal = $266,400

Issue Date FY: 2013 ( Subtotal = $255,744 )
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	11	5/16/2013	NON-COMPETING CONTINUATION	$15,984
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	11	3/21/2013	NON-COMPETING CONTINUATION	$239,760
														Subtotal = $255,744

Issue Date FY: 2012 ( Subtotal = $266,400 )
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	10	3/16/2012	NON-COMPETING CONTINUATION	$266,400
														Subtotal = $266,400

Issue Date FY: 2011 ( Subtotal = $266,400 )
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	001	9	5/31/2011	COMPETING CONTINUATION	$266,400
2011	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	8	5/27/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $266,400

Issue Date FY: 2009 ( Subtotal = $233,350 )
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	8	8/17/2009	NON-COMPETING CONTINUATION	$233,350
														Subtotal = $233,350

Issue Date FY: 2008 ( Subtotal = $233,350 )
2008	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	7	9/2/2008	NON-COMPETING CONTINUATION	$233,350
														Subtotal = $233,350

Issue Date FY: 2007 ( Subtotal = $238,112 )
2007	2007	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	6	8/21/2007	NON-COMPETING CONTINUATION	$238,112
														Subtotal = $238,112

Issue Date FY: 2006 ( Subtotal = $245,224 )
2006	2006	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	5	8/31/2006	NON-COMPETING CONTINUATION	$245,224
														Subtotal = $245,224

Issue Date FY: 2005 ( Subtotal = $251,125 )
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	4	9/27/2005	COMPETING CONTINUATION	$251,125
														Subtotal = $251,125

Issue Date FY: 2003 ( Subtotal = $216,000 )
2003	2003	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Drug Use and Addiction Research Programs	000	3		NON-COMPETING CONTINUATION	$216,000
														Subtotal = $216,000

Issue Date FY: 2002 ( Subtotal = $216,188 )
2002	2002	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Use and Addiction Research Programs	000	2	4/19/2002	NON-COMPETING CONTINUATION	$216,188
														Subtotal = $216,188

Issue Date FY: 2001 ( Subtotal = $216,938 )
2001	2001	WAKE FOREST UNIVERSITY SCHOOL OF MEDICINE	MEDICAL CENTER BOULEVARD	WINSTON-SALEM	NC	27157		USA	Drug Use and Addiction Research Programs	000	1	2/26/2001	NEW	$216,938
														Subtotal = $216,938

Grand Total All Awards = $3,155,352

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Animal Models of Cocaine Addiction

Award Number: R01DA014030

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2011

PERIOD OF PERFORMANCE END DATE: 03/31/2018

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