Psychostimulant-induced changes in locomotion involve activation of the 1B subtype of the a 1 -adrenoceptor (a 1B-AR). A key gap in our knowledge base is the functional characterization of the a 1A-AR subtype for the behavioral actions of cocaine and other psychostimulants. This R21 application seeks to characterize the involvement of brain alpha1 -AR subtypes in the behavioral actions of cocaine and amphetamine in rats using a novel apparatus/procedure to concurrently assess feeding and locomotion. Adult male rats will receive systemic injections of cocaine hydrochloride (0, 2.5, 5.0,10.0, and 20.0 mg/kg, IP) or D-amphetamine sulfate (0, 0.25, 0.5,1.0, and 2.0 mg/kg, IP) five minutes after bilateral ICV injections (0, 3 or 30 nMol/rat) of either an alpha1A antagonist [5-methyl-urapadil] or an alpha1B antagonist [L-765,314].
Aim 1 will characterize the effects of systemic cocaine (Exp 1) or amphetamine (Exp 2) on eating and locomotion in rats pretreated (ICV) with either vehicle, 5-methyl-urapadil or L-765,314. Activation of alpha1-ARs within the hypothalamic paraventricular nucleus (PVN) evokes hypophagia.
Aim 2 will characterize the role(s) of PVN alpha1-AR subtypes in cocaine-induced changes in feeding and locomotion. Dose-effect curves for changes in hypophagia and locomotion will be compared in rats receiving bilateral intra-PVN infusions of vehicle or 5-methyl-urapadil or L-765,314 (1 or 3 nMol/rat) followed by systemic doses of either cocaine (Exp 3), amphetamine (Exp 4). Insofar as dopamine neurons within the mesolimbic system modulate locomotion and are modulated by .1-ARs, the focus of Aim 3 is to characterize the differential involvement of alpha1 -AR subtypes within the core and shell regions of the nucleus accumbens (NAcc) for the hypophagic and locomotor actions of psychostimulants. In Experiments 5 and 6, systemic injections of cocaine or amphetamine will be preceded by bilateral injections of vehicle or of 5-methyl-urapadil or L-765,314 (1 or 3 nMol/rat) into one of three NAcc regions (rostral shell, caudal shell or core). These studies will advance our understanding of the behavioral functions of brain a l-AR subtypes and may lead to the identification of new drugs that inhibit eating without activating brain reinforcement systems.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DA017230-01A2
Application #
6921537
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Volman, Susan
Project Start
2005-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
1
Fiscal Year
2005
Total Cost
$216,430
Indirect Cost
Name
Texas A&M University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
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Wellman, Paul J; Davis, Kristina W; Clifford, P Shane et al. (2009) Changes in feeding and locomotion induced by amphetamine analogs in rats. Drug Alcohol Depend 100:234-9
Wellman, Paul J; Elliott, Audrea E; Barbee, Stephanie et al. (2008) Lobeline attenuates progressive ratio breakpoint scores for intracranial self-stimulation in rats. Physiol Behav 93:952-7
Wellman, Paul J; Hollas, Chelsie N; Elliott, Audrea E (2008) Systemic ghrelin sensitizes cocaine-induced hyperlocomotion in rats. Regul Pept 146:33-7
Wellman, Paul J; Ho, Dao H; Nation, Jack R (2008) Differential impact of cocaine on meal patterns in female and male rats. Life Sci 82:359-66
Wellman, Paul J; Nation, Jack R; Davis, Kristina W (2007) Impairment of acquisition of cocaine self-administration in rats maintained on a high-fat diet. Pharmacol Biochem Behav 88:89-93
Clifford, P Shane; Davis, Kristina W; Elliott, Audrea E et al. (2007) Effects of ICV administration of the alpha1A-adrenoceptor antagonist 5-methylurapidil on concurrent measures of eating and locomotion after cocaine in the rat. Life Sci 81:1059-65
Davis, Kristina W; Wellman, Paul J; Clifford, P Shane (2007) Augmented cocaine conditioned place preference in rats pretreated with systemic ghrelin. Regul Pept 140:148-52
Wellman, Paul J; Ho, Dao H; Davis, Kristina W (2005) Concurrent measures of feeding and locomotion in rats. Physiol Behav 84:769-74