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HUMAN COCAINE DISCRIMINATION

Award Number: R01DA010325
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: HEALTH SERVICES
PERIOD OF PERFORMANCE START DATE: 03/01/1997
PERIOD OF PERFORMANCE END DATE: 06/30/2007

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HUMAN COCAINE DISCRIMINATION - DESCRIPTION (provided by applicant): The present application is a request for continued funding of a project entitled "Cocaine Discrimination in Humans: Pharmacological Specificity" (DA010325). Recent data indicate that nearly 2 million Americans used cocaine in the past month. Alarmingly, between 1991 and 2001 the number of 8th, 10th, and 12th graders that reported using cocaine in the past 30 days increased 140, 86, and 50 percent, respectively. Thus, cocaine abuse continues to represent a significant public health concern, and will likely remain a problem for the foreseeable future. Intensive research efforts have been aimed at elucidating the neuropharmacological mechanisms that mediate the effects of cocaine. Drug-discrimination studies with laboratory animals that used the substitution and pretreatment methodologies have implicated a prominent role of dopamine in mediating the effects of cocaine. During the initial funding period of this project we used a drug discrimination task and the substitution methodology to demonstrate that dopamine systems are involved in mediating the discriminative-stimulus effects of cocaine in humans. We are not aware of any published studies in which the discriminative-stimulus effects of cocaine were assessed in humans following pretreatment with another drug even though drug-discrimination procedures may be particularly well suited for studying agonist-antagonist interactions. The aim of this application is to further characterize the role of dopamine in mediating the discriminative-stimulus effects of cocaine in humans using a pretreatment methodology. To accomplish this aim, 3 laboratory experiments will be conducted with volunteers with histories of cocaine abuse. The discriminative-stimulus and subjective effects of cocaine will be assessed alone and following pretreatment with mazindol, a dopamine uptake blocker (Exp. 1); fluphenazine, a D1-D2 dopamine receptor antagonist (Exp. 2); and haloperidol, a D2 dopamine receptor antagonist (Exp. 3). We predict that pretreating volunteers with a dopamine agonist or antagonist will shift the cocaine dose-response curve, leftward and rightward, respectively. The experiments proposed in this "proof-of-concept" continuation application will provide additional information concerning the role of dopamine in mediating the discriminative-stimulus effects of cocaine in humans. Elucidating the role of dopamine in mediating the effects of cocaine may guide the development of pharmacological interventions for cocaine.


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: 2006 ( Subtotal = $215,758 )
2006	2006	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	10	6/23/2006	NON-COMPETING CONTINUATION	$215,758
														Subtotal = $215,758

Issue Date FY: 2005 ( Subtotal = $220,950 )
2005	2005	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	9	7/30/2005	NON-COMPETING CONTINUATION	$220,950
														Subtotal = $220,950

Issue Date FY: 2004 ( Subtotal = $220,500 )
2004	2004	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	8	7/1/2004	NON-COMPETING CONTINUATION	$220,500
														Subtotal = $220,500

Issue Date FY: 2003 ( Subtotal = $219,000 )
2003	2003	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	7	7/31/2003	COMPETING CONTINUATION	$219,000
														Subtotal = $219,000

Issue Date FY: 2001 ( Subtotal = $254,236 )
2001	2001	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	6	1/15/2001	NON-COMPETING CONTINUATION	$254,236
														Subtotal = $254,236

Issue Date FY: 2000 ( Subtotal = $246,829 )
2000	2000	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	5	2/10/2000	NON-COMPETING CONTINUATION	$246,829
														Subtotal = $246,829

Issue Date FY: 1999 ( Subtotal = $196,441 )
1999	1999	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Drug Use and Addiction Research Programs	000	4	7/30/1999	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$149,478
1999	1999	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Drug Use and Addiction Research Programs	000	3	7/30/1999	NON-COMPETING CONTINUATION	$46,963
														Subtotal = $196,441

Issue Date FY: 1998 ( Subtotal = $190,719 )
1998	1998	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 NORTH STATE STREET	JACKSON	MS	39216	HINDS	USA	Drug Use and Addiction Research Programs	000	2	2/27/1998	NON-COMPETING CONTINUATION	$190,719
														Subtotal = $190,719

Grand Total All Awards = $1,764,433

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HUMAN COCAINE DISCRIMINATION

Award Number: R01DA010325

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: HEALTH SERVICES

PERIOD OF PERFORMANCE START DATE: 03/01/1997

PERIOD OF PERFORMANCE END DATE: 06/30/2007

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