Stress is believed to be an etiological factor in the abuse of ethanol. However, the role of stress in the risk for excessive ethanol consumption is difficult to untangle from the stress derived from excessively drinking alcohol. A starting point is to operationally define stress as activation of the hypothalamic-pituitaryadrenal (HPA) axis through measurable changes in circulating levels of the hormones adrenocorticotropin (ACTH) from the pituitary and cortisol from the adrenals. Monkeys show clear individual differences in endocrine response of the HPA axis to stressful events and also clear individual differences in the amount of ethanol they choose to self-administer. To address the causal interaction of stress and excessive ethanol interaction, we propose to characterize individual differences in HPA response to stress prior to, during and following chronic ethanol self administration. Further, the very nature of endocrine response to stress brings into focus the concept of neurocircuitries underlying information flow, integration and functional output. Viewing the HPA response as an intermediate determinant of behavior guides a translational endeavor into the realm of intermediate phenotypes or """"""""endophenotypes"""""""". To address the predictive validity of an HPA response as an endophenotype underlying the risk of excessive ethanol self-administration, we will screen a large population of monkeys for specific HPA responses. Individuals that are on the extreme ends of the population distribution of the potential endophenotype will be characterized in the ethanol self-administration procedure. Finally, we will screen gene polymorphisms to identify those associated with an HPA response endophenotype. We will assess the predictive value of the genetic polymorphisms by screening the rhesus colony to select animals with the """"""""risk"""""""" alleles and then characterize them in the alcohol self administration procedure.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA013510-10
Application #
7760980
Study Section
Special Emphasis Panel (ZAA1-DD (71))
Program Officer
Grandison, Lindsey
Project Start
2002-02-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
10
Fiscal Year
2010
Total Cost
$581,084
Indirect Cost
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Cervera-Juanes, Rita; Wilhelm, Larry J; Park, Byung et al. (2017) Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals differentiating low/binge from heavy alcohol drinking. Alcohol 60:103-113
Cuzon Carlson, Verginia C; Grant, Kathleen A; Lovinger, David M (2017) Synaptic adaptations to chronic ethanol intake in male rhesus monkey dorsal striatum depend on age of drinking onset. Neuropharmacology 131:128-142
Jimenez, Vanessa A; Allen, Daicia C; McClintick, Megan N et al. (2017) Social setting, social rank and HPA axis response in cynomolgus monkeys. Psychopharmacology (Berl) 234:1881-1889
Cervera-Juanes, R; Wilhelm, L J; Park, B et al. (2017) Alcohol-dose-dependent DNA methylation and expression in the nucleus accumbens identifies coordinated regulation of synaptic genes. Transl Psychiatry 7:e994
Jimenez, Vanessa A; Grant, Kathleen A (2017) Studies using macaque monkeys to address excessive alcohol drinking and stress interactions. Neuropharmacology 122:127-135
Turecek, Josef; Han, Victor Z; Cuzon Carlson, Verginia C et al. (2016) Electrical Coupling and Synchronized Subthreshold Oscillations in the Inferior Olive of the Rhesus Macaque. J Neurosci 36:6497-502
Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T et al. (2016) Chronic ethanol self-administration in macaques shifts dopamine feedback inhibition to predominantly D2 receptors in nucleus accumbens core. Drug Alcohol Depend 158:159-63
Pleil, Kristen E; Helms, Christa M; Sobus, Jon R et al. (2016) Effects of chronic alcohol consumption on neuronal function in the non-human primate BNST. Addict Biol 21:1151-1167
McClintick, Megan N; Grant, Kathleen A (2016) Aggressive temperament predicts ethanol self-administration in late adolescent male and female rhesus macaques. Psychopharmacology (Berl) 233:3965-3976
Siciliano, Cody A; Calipari, Erin S; Yorgason, Jordan T et al. (2016) Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques. Psychopharmacology (Berl) 233:1435-43

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