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Neuropharmacological mechanisms of stress-induced relapse to alcohol

Award Number: R01AA024341
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2015
PERIOD OF PERFORMANCE END DATE: 05/31/2022

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Neuropharmacological mechanisms of stress-induced relapse to alcohol - DESCRIPTION (provided by applicant): Stressful life events are associated with increased alcohol intake and relapse in humans. We have studied, using animal models, the brain mechanisms underlying such reinstatement for many years and have recently found that prazosin, an alpha-1 adrenoceptor antagonist, blocks reinstatement induced by the stressors intermittent footshock and yohimbine. Both of these stressors have been extensively used in studies on stress-induced alcohol seeking. In the present proposal, we wish to extend these findings to the kappa opioid receptor agonist U50,488 (U50), a compound that also induced stress-like effects, and that can induce reinstatement of alcohol, nicotine and other drugs. Since alcohol dependence affects responses to stressors and to the drugs used to treat alcoholism, we will assess in Aim 1 the effects of alcohol dependence on footshock- and U50-induced reinstatement and then if dependence affects blockade of footshock and U50-induced reinstatement by prazosin. In Aim 2 we will determine the effects of prazosin on neuronal activation (assessed by induction of the immediate early gene protein product Fos) induced by these stressors in a mapping study. The Fos data will be used as a guide for studies with intracranial injections of prazosin to determine the brain sites in which it blocks stress-induced relapse. In Aim 3 we will use a novel neuropharmacogenetic approach (the Daun02 inactivation method) to identify activated neurons in specific brain areas that play causal roles in footshock- and U50-induced reinstatement of alcohol seeking. These studies will provide information on the neuronal mechanisms that underlie stress-induced alcohol seeking. Such data will be useful in two major ways: 1) understanding the mechanisms by which footshock and U50 produce relapse to alcohol seeking and 2) guiding the development of treatment strategies for the prevention of relapse.


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: 2023 ( Subtotal = $0 )
2023	2019	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Alcohol Research Programs	000	5	10/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON			CAN	Alcohol Research Programs	000	5	5/4/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $193,467 )
2019	2019	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Alcohol Research Programs	000	5	5/23/2019	NON-COMPETING CONTINUATION	$193,467
														Subtotal = $193,467

Issue Date FY: 2018 ( Subtotal = $193,467 )
2018	2018	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Alcohol Research Programs	000	4	5/9/2018	NON-COMPETING CONTINUATION	$193,467
														Subtotal = $193,467

Issue Date FY: 2017 ( Subtotal = $193,467 )
2017	2017	CENTRE FOR ADDICTION AND MENTAL HEALTH	1001 QUEEN ST W	TORONTO	ON	M6J 1H4		CAN	Alcohol Research Programs	000	3	5/31/2017	NON-COMPETING CONTINUATION	$193,467
														Subtotal = $193,467

Issue Date FY: 2016 ( Subtotal = $193,467 )
2016	2016	CENTRE FOR ADDICTION & MENTAL HEALTH	1001 Queen Street West and 60 White	TORONTO				CAN	Alcohol Research Programs	000	2	5/18/2016	NON-COMPETING CONTINUATION	$193,467
														Subtotal = $193,467

Issue Date FY: 2015 ( Subtotal = $193,467 )
2015	2015	CENTRE FOR ADDICTION & MENTAL HEALTH	1001 Queen Street West and 60 White	TORONTO				CAN	Alcohol Research Programs	000	1	8/4/2015	NEW	$193,467
														Subtotal = $193,467

Grand Total All Awards = $967,335

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Neuropharmacological mechanisms of stress-induced relapse to alcohol

Award Number: R01AA024341

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2015

PERIOD OF PERFORMANCE END DATE: 05/31/2022

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