Withdrawal from acute alcohol exposure produces profound changes in behavior including reduced exploration and locomotor activity as well as suppressed social interaction. These behavioral changes characterize the """"""""hangover"""""""" state and are remarkably similar to sickness behaviors that are typically observed during acute illness produced by infectious agents or injection of pro-inflammatory cytokines. We therefore propose that behavioral responses during withdrawal from acute alcohol exposure in rats may be viewed as sickness-like behavioral responses that are initiated and maintained by activation of inflammatory-related pathways traditionally associated with immune activation. Our preliminary data indicate robust increases in transcriptional activity of interleukin-1 in CNS sites that are crucial for normal progression of the immune response and the generation of sickness behaviors. The goal of the following proposal, therefore, is to (Aim 1) establish the temporal and spatial characteristics of cytokine responses produced by hangover, (Aim 2) to identify probable cellular and neurochemical mechanisms of cytokine responses produced by hangover, and (Aim 3) to forge a positive mechanistic link between increased central cytokines and the sickness-like behavioral changes observed during hangover in rats.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AA016305-02
Application #
7586260
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Cui, Changhai
Project Start
2008-03-15
Project End
2010-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
2
Fiscal Year
2009
Total Cost
$181,688
Indirect Cost
Name
State University of NY, Binghamton
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
090189965
City
Binghamton
State
NY
Country
United States
Zip Code
13902
Bordner, Kelly; Deak, Terrence (2015) Endogenous opioids as substrates for ethanol intake in the neonatal rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period. Physiol Behav 148:100-10
Doremus-Fitzwater, Tamara L; Buck, Hollin M; Bordner, Kelly et al. (2014) Intoxication- and withdrawal-dependent expression of central and peripheral cytokines following initial ethanol exposure. Alcohol Clin Exp Res 38:2186-98
Richey, Laura; Doremus-Fitzwater, Tamara L; Buck, Hollin M et al. (2012) Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure. Pharmacol Biochem Behav 103:284-94
Wright, Andrew J; Deak, Terrence; Parsons, E C M (2011) Size matters: management of stress responses and chronic stress in beaked whales and other marine mammals may require larger exclusion zones. Mar Pollut Bull 63:5-9
Buck, Hollin M; Hueston, Cara M; Bishop, Christopher et al. (2011) Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses to stress challenges imposed during withdrawal from acute alcohol exposure in Sprague-Dawley rats. Psychopharmacology (Berl) 218:203-15
Arakawa, Hiroyuki; Blandino Jr, Peter; Deak, Terrence (2009) Central infusion of interleukin-1 receptor antagonist blocks the reduction in social behavior produced by prior stressor exposure. Physiol Behav 98:139-46
Deak, Terrence; Arakawa, Hiroyuki; Bekkedal, Marni Y V et al. (2009) Validation of a novel social investigation task that may dissociate social motivation from exploratory activity. Behav Brain Res 199:326-33
Deak, Terrence (2008) Immune cells and cytokine circuits: toward a working model for understanding direct immune-to-adrenal communication pathways. Endocrinology 149:1433-5