The discriminative stimulus properties of alcohol may contribute to its abuse and addiction potential in humans. Animal models of alcohol discrimination have indicated the involvement of serotonin (5-HT) receptors, including the G/i/o-coupled 5-HT/lB/D receptors, in mediating the discriminative stimulus properties of alcohol. The main hypothesis of the proposed pilot study is that the acquisition of ethanol discrimination in rats is associated with changes in 5-HT/l receptor activity. A technique has been developed in our laboratory, whereby receptor-coupled G-protein activity is measured by agonist-stimulated [35S]GTPgammaS autoradiography in tissue sections. This technique allows quantification of the biochemical activity of G-protein-coupled receptors with a high degree of anatomical resolution. This methodology is ideally suited to the study of the effects of the acquisition of ethanol discrimination on 5-HT1 receptor-coupled G-protein activity. Regions where changes in 5-HT1 receptor-coupled G-protein activity are observed autoradiographically will be dissected, and more quantitative biochemical and pharmacological analysis will be performed using both agonist-stimulated [35S]GTPgammaS binding and receptor binding in membranes. This approach, which combines behavioral pharmacology with neuroanatomy and signal transduction biochemistry, may elucidate the neuroadaptive role of 5-HTl receptors in the development of ethanol discrimination. This pilot project directly addresses the Center aims regarding the possible cellular mechanisms underlying ethanol's discriminative stimulus effects. It will provide import pilot data that can supplement the studies performed in Project 3 of the Center, as well as provide information for the R01 work conducted by Dr. Grant.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA011997-04
Application #
6563226
Study Section
Project Start
2002-01-01
Project End
2002-12-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
2002
Total Cost
$178,517
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Davenport, April T; Grant, Kathleen A; Szeliga, Kendall T et al. (2014) Standardized method for the harvest of nonhuman primate tissue optimized for multiple modes of analyses. Cell Tissue Bank 15:99-110
Freeman, Willard M; Vanguilder, Heather D; Guidone, Elizabeth et al. (2011) Plasma proteomic alterations in non-human primates and humans after chronic alcohol self-administration. Int J Neuropsychopharmacol 14:899-911
Lyn, Heidi; Pierre, Peter; Bennett, Allyson J et al. (2011) Planum temporale grey matter asymmetries in chimpanzees (Pan troglodytes), vervet (Chlorocebus aethiops sabaeus), rhesus (Macaca mulatta) and bonnet (Macaca radiata) monkeys. Neuropsychologia 49:2004-12
Graef, John D; Godwin, Dwayne W (2010) Intrinsic plasticity in acquired epilepsy: too much of a good thing? Neuroscientist 16:487-95
Freeman, Willard M; Salzberg, Anna C; Gonzales, Steven W et al. (2010) Classification of alcohol abuse by plasma protein biomarkers. Biol Psychiatry 68:219-22
Cheng, Heng-Jie; Grant, Kathleen A; Han, Qing-Hua et al. (2010) Up-regulation and functional effect of cardiac ?3-adrenoreceptors in alcoholic monkeys. Alcohol Clin Exp Res 34:1171-81
McCauley, Anita K; Frank, Steven T; Godwin, Dwayne W (2009) Brainstem nitrergic innervation of the mouse visual thalamus. Brain Res 1278:34-49
Shively, Carol A; Mietus, Joseph E; Grant, Kathleen A et al. (2007) Effects of chronic moderate alcohol consumption and novel environment on heart rate variability in primates (Macaca fascicularis). Psychopharmacology (Berl) 192:183-91
Walker, Stephen J; Wang, Yulei; Grant, Kathleen A et al. (2006) Long versus short oligonucleotide microarrays for the study of gene expression in nonhuman primates. J Neurosci Methods 152:179-89
Freeman, Willard M; Gooch, Randy S; Lull, Melinda E et al. (2006) Apo-AII is an elevated biomarker of chronic non-human primate ethanol self-administration. Alcohol Alcohol 41:300-5

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