The long-range goals of this project are to identify CNS sites, neurotransmitter systems and receptors involved in mediating the actions of ethanol (E) and promoting high alcohol-seeking behavior. The overall hypothesis to be tested is that there are innate neurobiological differences within key CNS limbic structures which underlie genetic vulnerability to high alcohol drinking behavior. The objectives of this proposal are to determine (1) the effects of chronic alcohol consumption on neuronal activity within limbic and other important CNS structures; (2) the effects of E drinking conditions on altering neuronal activity within limbic and other important CNS structures; (3) the involvement of ventral tegmental area (VTA) dopamine (DA) neurons, and (5-HT) serotonin transmission and 5-HT3 receptors in alcohol-seeking behavior; and (4) differences between rat lines, selectively bred for disparate alcohol drinking behaviors, in GABAA and 5-HT3 receptor regulation of VTA mediated reinforcement processes. The overall hypothesis will be tested in the alcohol-preferring P, alcohol-nonpreferring NP, high alcohol-drinking HAD and low alcohol-drinking LAD lines. The [14C]-2-deoxyglucose (2-DG) uptake procedure coupled to quantitative autoradiography will be employed to assess changes in regional CNS neuronal activity of P and HAD rats that may be associated with chronic alcohol drinking and alcohol drinking conditions. In vivo microdialysis will be used to measure changes in extracellular levels of DA and 5-HT in the VTA and/or nucleus accumbens (ACB) to examine the effects of local E and 5-HT3 agonist administration, and alcohol drinking conditions on DA and 5-HT neuronal activity. The intracranial self-administration (ICSA) procedure will be utilized to examine line differences in reinforcement processes mediated by GABAA and 5-HT3 receptors within the VTA. The results of this project will provide fundamental information toward understanding the neurobiological mechanisms underlying high alcohol-seeking behavior. Such information would be important for developing pharmacotherapies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010721-09
Application #
6644856
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (04))
Program Officer
Egli, Mark
Project Start
1995-08-01
Project End
2005-08-31
Budget Start
2003-09-01
Budget End
2004-08-31
Support Year
9
Fiscal Year
2003
Total Cost
$298,000
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
McBride, William J; Rodd, Zachary A; Bell, Richard L et al. (2014) The alcohol-preferring (P) and high-alcohol-drinking (HAD) rats--animal models of alcoholism. Alcohol 48:209-15
Ding, Zheng-Ming; Rodd, Zachary A; Engleman, Eric A et al. (2013) Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats. Addict Biol 18:297-306
Jung, Young-Chul; Chanraud, Sandra; Sullivan, Edith V (2012) Neuroimaging of Wernicke's encephalopathy and Korsakoff's syndrome. Neuropsychol Rev 22:170-80
Hauser, Sheketha R; Getachew, Bruk; Oster, Scott M et al. (2012) Nicotine modulates alcohol-seeking and relapse by alcohol-preferring (P) rats in a time-dependent manner. Alcohol Clin Exp Res 36:43-54
Ding, Zheng-Ming; Engleman, Eric A; Rodd, Zachary A et al. (2012) Ethanol increases glutamate neurotransmission in the posterior ventral tegmental area of female wistar rats. Alcohol Clin Exp Res 36:633-40
Deehan Jr, Gerald A; McKinzie, David L; Carroll, F Ivy et al. (2012) The long-lasting effects of JDTic, a kappa opioid receptor antagonist, on the expression of ethanol-seeking behavior and the relapse drinking of female alcohol-preferring (P) rats. Pharmacol Biochem Behav 101:581-7
Ding, Zheng-Ming; Oster, Scott M; Hauser, Sheketha R et al. (2012) Synergistic self-administration of ethanol and cocaine directly into the posterior ventral tegmental area: involvement of serotonin-3 receptors. J Pharmacol Exp Ther 340:202-9
Dhaher, Ronnie; Toalston, Jamie E; Hauser, Sheketha R et al. (2012) Effects of naltrexone and LY255582 on ethanol maintenance, seeking, and relapse responding by alcohol-preferring (P) rats. Alcohol 46:17-27
Getachew, Bruk; Hauser, Sheketha R; Dhaher, Ronnie et al. (2011) CB1 receptors regulate alcohol-seeking behavior and alcohol self-administration of alcohol-preferring (P) rats. Pharmacol Biochem Behav 97:669-75
Ding, Zheng-Ming; Oster, Scott M; Hall, Sarah R et al. (2011) The stimulating effects of ethanol on ventral tegmental area dopamine neurons projecting to the ventral pallidum and medial prefrontal cortex in female Wistar rats: regional difference and involvement of serotonin-3 receptors. Psychopharmacology (Berl) 216:245-55

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