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Nucleus accumbens processing of reward-predictive cues

Award Number: R01DA019473
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2006
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Nucleus accumbens processing of reward-predictive cues - Project Summary Salient sensory events can elevate the arousal level, increasing the subject's readiness to engage motor, cognitive and attentional resources. For example, arousal is increased when a sleeping person is shaken awake, or when a quiescent rat is transferred to a new cage or otherwise handled. Recent evidence shows that the dopamine projection from the midbrain ventral tegmental area to the nucleus accumbens (NAc) core serves to elevate arousal in response to such events, and that this effect likely involves both D1 and D2 dopamine receptor- expressing NAc neurons. Yet, this role for mesolimbic circuitry in arousal has not been reconciled with the large literature that interprets the behavioral effects of NAc dopamine manipulations as the result of altered motivation or reward. To investigate how arousal might contribute to the reward-seeking effects of dopamine, we first established a behavioral paradigm in which rats' performance of a cued operant task declines over time due to gradually decreasing arousal. We find that simply handling the animal for a few seconds dramatically restores high levels of performance for many minutes. Handling also increases dopamine levels in the NAc and the firing response of NAc neurons to reward-predictive cues, which are known to be dopamine-dependent and causal to the cued reward-seeking behavioral response. These results suggest that the dopamine increase caused by arousing events facilitates reward seeking. This is one of the major hypotheses tested in this proposal. This hypothesis suggests an even more provocative idea: that NAc dopamine promotes reward seeking by increasing arousal. If that were the case, then dopamine should act via the same local circuit mechanism within the NAc to increase both arousal and reward seeking. Previous studies point towards (but do not conclusively demonstrate) a specific circuit mechanism common to both processes: D1 neurons are the “effector” neurons whose firing drives both arousal and reward seeking, whereas D2 neurons strongly inhibit D1 neurons. Dopamine promotes arousal and reward seeking primarily by acting at the D2 receptor to reduce the inhibitory drive from D2 neurons onto D1 neurons, and only secondarily (if at all) by directly increasing the excitability of D1 neurons by acting at the D1 receptor. This circuit model receives a great deal of indirect support from disparate published experiments, as well as our pilot experiments, that have tested individual components of the model in isolation from the others. In this proposal, we aim to test the model cohesively and thoroughly, and in doing so, to establish that dopamine increases both arousal and reward seeking by the same local NAc circuit mechanism. Doing so will reframe current thinking regarding the behavioral role of mesolimbic dopamine in two ways; first, by establishing the causal contribution of D2 neurons' inhibition of D1 neurons (and the relief of this inhibition by dopamine) to both arousal and reward seeking; and second, by showing that dopamine facilitates arousal and reward seeking via the same local circuit mechanism – which will introduce the field to the hypothesis that dopamine's well-known ability to promote reward seeking could be due in part to increased arousal.


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: 2024 ( Subtotal = $654,254 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	003	20	6/21/2024	NON-COMPETING CONTINUATION	$654,254
2024	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	19	10/24/2023	COMPETING CONTINUATION	$0
2024	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	002	19	6/4/2024	COMPETING CONTINUATION	$12,269
2024	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	001	18	6/4/2024	NON-COMPETING CONTINUATION	-$12,269
														Subtotal = $654,254

Issue Date FY: 2023 ( Subtotal = $686,900 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	001	19	9/21/2023	COMPETING CONTINUATION	$686,900
2023	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	18	9/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $686,900

Issue Date FY: 2022 ( Subtotal = $399,462 )
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	001	18	3/18/2022	NON-COMPETING CONTINUATION	$39,948
2022	2022	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	18	3/10/2022	NON-COMPETING CONTINUATION	$359,514
														Subtotal = $399,462

Issue Date FY: 2021 ( Subtotal = $399,462 )
2021	2021	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	17	3/3/2021	NON-COMPETING CONTINUATION	$399,462
														Subtotal = $399,462

Issue Date FY: 2020 ( Subtotal = $399,462 )
2020	2020	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	16	2/26/2020	NON-COMPETING CONTINUATION	$399,462
														Subtotal = $399,462

Issue Date FY: 2019 ( Subtotal = $399,462 )
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	002	15	2/22/2019	NON-COMPETING CONTINUATION	$399,462
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	004	15	3/19/2019	NON-COMPETING CONTINUATION	$399,462
2019	2019	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	003	15	3/13/2019	NON-COMPETING CONTINUATION	-$399,462
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	13	2/15/2019	COMPETING CONTINUATION	-$143,967
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	001	14	2/15/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$143,967
2019	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	005	13	7/16/2019	COMPETING CONTINUATION	$0
														Subtotal = $399,462

Issue Date FY: 2018 ( Subtotal = $506,175 )
2018	2018	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	001	13	5/31/2018	COMPETING CONTINUATION	$506,175
2018	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Drug Use and Addiction Research Programs	000	12	1/12/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $506,175

Issue Date FY: 2016 ( Subtotal = $351,326 )
2016	2016	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Drug Use and Addiction Research Programs	002	12	3/16/2016	NON-COMPETING CONTINUATION	$351,326
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	001	10	12/3/2015	NON-COMPETING CONTINUATION	-$226,405
2016	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE INC	111 E 210TH ST	BRONX	NY	10467	BRONX	USA	Drug Use and Addiction Research Programs	000	11	12/3/2015	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$226,405
														Subtotal = $351,326

Issue Date FY: 2015 ( Subtotal = $395,609 )
2015	2015	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	10	3/3/2015	NON-COMPETING CONTINUATION	$395,609
														Subtotal = $395,609

Issue Date FY: 2014 ( Subtotal = $401,635 )
2014	2014	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	9	3/24/2014	NON-COMPETING CONTINUATION	$401,635
														Subtotal = $401,635

Issue Date FY: 2013 ( Subtotal = $366,148 )
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	002	8	4/11/2013	SUPPLEMENT FOR EXPANSION	$46,760
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	8	3/15/2013	NON-COMPETING CONTINUATION	$311,850
2013	2013	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	001	8	4/5/2013	NON-COMPETING CONTINUATION	$7,538
														Subtotal = $366,148

Issue Date FY: 2012 ( Subtotal = $333,500 )
2012	2012	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	7	3/23/2012	COMPETING CONTINUATION	$333,500
														Subtotal = $333,500

Issue Date FY: 2010 ( Subtotal = $312,766 )
2010	2010	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	6	3/5/2010	NON-COMPETING CONTINUATION	$312,766
														Subtotal = $312,766

Issue Date FY: 2009 ( Subtotal = $315,925 )
2009	2009	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	5	4/2/2009	NON-COMPETING CONTINUATION	$315,925
														Subtotal = $315,925

Issue Date FY: 2008 ( Subtotal = $315,925 )
2008	2008	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	4	3/12/2008	NON-COMPETING CONTINUATION	$315,925
														Subtotal = $315,925

Issue Date FY: 2007 ( Subtotal = $328,062 )
2007	2007	ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV	1300 MORRIS PARK AVENUE	BRONIX	NY	10461		USA	Drug Use and Addiction Research Programs	000	3	9/10/2007	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$328,062
2007	2007	ERNEST GALLO CLINIC & RESEARCH CENTER	5858 HORTON STREET, SUITE 200	EMERYVILLE	CA	94608	ALAMEDA	USA	Drug Use and Addiction Research Programs	000	2	3/27/2007	NON-COMPETING CONTINUATION	$0
														Subtotal = $328,062

Issue Date FY: 2006 ( Subtotal = $337,860 )
2006	2006	ERNEST GALLO CLINIC & RESEARCH CENTER	5858 HORTON STREET, SUITE 200	EMERYVILLE	CA	94608	ALAMEDA	USA	Drug Use and Addiction Research Programs	000	1	4/17/2006	NEW	$337,860
														Subtotal = $337,860

Grand Total All Awards = $6,903,933

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Nucleus accumbens processing of reward-predictive cues

Award Number: R01DA019473

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2006

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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