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mPFC, n. accumbens and and reinstatement of cocaine seeking

Award Number: R01DA015214
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/10/2003
PERIOD OF PERFORMANCE END DATE: 01/31/2013

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mPFC, n. accumbens and and reinstatement of cocaine seeking - DESCRIPTION (provided by applicant): This is the first resubmission of a competing renewal for the research grant R01 DA15214, a five-year project that activated on 07 February 2003. During the current funding period, our work focused on delineating the neuronal circuitry and associated neurotransmitter systems underlying cocaine priming-induced reinstatement of cocaine seeking and, to a lesser extent, cocaine reinforcement. Our work indicates that D1-like and D2 dopamine receptors in the shell, but not core, subregion of the nucleus accumbens play critical roles in the reinstatement of cocaine seeking and cocaine reinforcement. In addition, we demonstrated that administration of cocaine directly into the medial prefrontal cortex (mPFC) reinstates cocaine-seeking behavior by increasing AMPA-mediated glutamate transmission in the nucleus accumbens. Our research, combined with that of others, demonstrates that a collection of limbic nuclei, including the ventral tegmental area (VTA), nucleus accumbens, mPFC, amygdala, hippocampus and ventral pallidum, underlie cocaine reinforcement and the reinstatement of cocaine seeking. In Specific Aims 1 and 2 of the present application, we extend this circuitry to include the pedunculopontine tegmental nucleus (PPTg), which receives glutamatergic inputs from the mPFC and sends glutamatergic and cholinergic projections to the VTA that synapse on dopaminergic neurons. The overarching hypothesis of these experiments is that the serial circuit encompassing the mPFC, PPTg, VTA and nucleus accumbens is critically involved in cocaine reinforcement as well as cocaine priming-induced reinstatement of drug seeking. We also propose to examine a practical application for the emerging neuronal circuitry underlying cocaine reinforcement and reinstatement. Thus, in Specific Aim 3 we will assess the effect of reversible inactivation of various limbic nuclei on cocaine reinforcement and reinstatement of cocaine seeking. The novel aspect of this aim is the method of neuronal inactivation. We will utilize deep brain stimulation (DBS), a technique increasingly used clinically for the treatment of neurological diseases that has recently been tested as a potential treatment for a range of psychiatric disorders as well. Cocaine addiction remains a major public health issue in the United Sates. The experiments described in this grant application are designed to delineate the neuronal circuitry and associated neurotransmitter systems underlying influenced by cocaine using animal models. The overarching goal of this project is to identify novel therapeutic targets for cocaine craving and addiction.


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: 2019 ( Subtotal = -$1,372 )
2019	2018	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	16	9/26/2019	NON-COMPETING CONTINUATION	-$1,372
														Subtotal = -$1,372

Issue Date FY: 2018 ( Subtotal = $335,616 )
2018	2018	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	16	5/16/2018	NON-COMPETING CONTINUATION	$335,616
														Subtotal = $335,616

Issue Date FY: 2017 ( Subtotal = $335,052 )
2017	2017	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	15	5/23/2017	NON-COMPETING CONTINUATION	$335,052
														Subtotal = $335,052

Issue Date FY: 2016 ( Subtotal = $331,158 )
2016	2016	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	14	5/2/2016	NON-COMPETING CONTINUATION	$331,158
														Subtotal = $331,158

Issue Date FY: 2015 ( Subtotal = $328,962 )
2015	2015	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	13	5/1/2015	NON-COMPETING CONTINUATION	$328,962
														Subtotal = $328,962

Issue Date FY: 2014 ( Subtotal = $333,457 )
2014	2014	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	12	5/22/2014	COMPETING CONTINUATION	$333,457
														Subtotal = $333,457

Issue Date FY: 2012 ( Subtotal = $305,550 )
2012	2012	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	11	1/27/2012	NON-COMPETING CONTINUATION	$305,550
														Subtotal = $305,550

Issue Date FY: 2011 ( Subtotal = $305,550 )
2011	2011	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	001	10	5/27/2011	NON-COMPETING CONTINUATION	$22,050
2011	2011	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	10	1/28/2011	NON-COMPETING CONTINUATION	$283,500
														Subtotal = $305,550

Issue Date FY: 2010 ( Subtotal = $311,850 )
2010	2010	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	000	9	1/20/2010	NON-COMPETING CONTINUATION	$311,850
														Subtotal = $311,850

Issue Date FY: 2009 ( Subtotal = $384,830 )
2009	2009	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	003	8	4/23/2009	NON-COMPETING CONTINUATION	$31,500
2009	2009	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	002	8	2/25/2009	NON-COMPETING CONTINUATION	$283,500
2009	2009	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	004	8	8/12/2009	SUPPLEMENT FOR EXPANSION	$69,829
2009	2008	UNIVERSITY OF PENNSYLVANIA	3451 WALNUT STREET	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Drug Use and Addiction Research Programs	001	7	2/5/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$144,541
2009	2008	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	6	2/5/2009	COMPETING CONTINUATION	-$144,540
														Subtotal = $384,830

Issue Date FY: 2008 ( Subtotal = $325,000 )
2008	2008	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	6	1/29/2008	COMPETING CONTINUATION	$325,000
														Subtotal = $325,000

Issue Date FY: 2007 ( Subtotal = $229,697 )
2007	2007	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	5	4/27/2007	NON-COMPETING CONTINUATION	$229,697
														Subtotal = $229,697

Issue Date FY: 2006 ( Subtotal = $236,557 )
2006	2006	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	4	1/13/2006	NON-COMPETING CONTINUATION	$236,557
														Subtotal = $236,557

Issue Date FY: 2005 ( Subtotal = $242,250 )
2005	2005	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	3	1/31/2005	NON-COMPETING CONTINUATION	$242,250
														Subtotal = $242,250

Issue Date FY: 2004 ( Subtotal = $242,250 )
2004	2004	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	2	2/2/2004	NON-COMPETING CONTINUATION	$242,250
														Subtotal = $242,250

Issue Date FY: 2003 ( Subtotal = $267,250 )
2003	2003	BOSTON UNIVERSITY	25 BUICK STREET	BOSTON	MA	02215	SUFFOLK	USA	Drug Use and Addiction Research Programs	000	1		NEW	$267,250
														Subtotal = $267,250

Grand Total All Awards = $4,513,657

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mPFC, n. accumbens and and reinstatement of cocaine seeking

Award Number: R01DA015214

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/10/2003

PERIOD OF PERFORMANCE END DATE: 01/31/2013

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