The long range goals of this project are to identify CNS sites, receptors and neurotransmitter systems involved in mediating the rewarding properties of alcohol. The overall hypotheses to be tested in the present proposal are that the posterior ventral tegmental area (VTA) dopamine (DA) neuronal system plays a major role in mediating ethanol (E) reinforcement and there is a relationship between the reinforcing properties of E in the posterior VTA and innate high alcohol drinking behavior. In support of these hypotheses, initial data indicate that Wistar rats will self-administer E directly into the posterior VTA and that self-infusion of E into the VTA is significantly different between lines of rats selectively bred for disparate alcohol drinking behaviors. However, E reinforcement in the VTA has not been fully characterized and it is not known if DA neurons may be mediating E reinforcement within the posterior VTA nor what receptors may be involved. The objectives of this proposal are to 1) characterize the reinforcing properties of E within the VTA of selectively-bred alcohol preferring P, alcohol non-preferring NP, high alcohol-drinking HAD and low alcohol drinking LAD lines of rats, and Wistar rats; 2) establish the involvement of VTA DA neurons and GABA A and 5HT3 receptors in mediating E reinforcement within the posterior VTA; and 3) examine the influence of alcohol drinking on the reinforcing effects of E within the posterior VTA. The technique of intra-cranial self- administration (ICSA) will be used to assess E reinforcement within the VTA. Microdialysis procedures will be used to measure changes in the extracellular levels of DA in the n. accumbens (ACB) as an index of VTA neuronal activity. Pharmacological studies will be undertaken to determine the effects of co-infusing D2, GABAA and 5HT3 receptor agents with alcohol in the posterior VTA on ICSA behavior. The results will establish a relationship between alcohol drinking and the reinforcing effects of E in the posterior VTA and will provide important information on neurotransmitter systems and receptors mediating the reinforcing actions of alcohol, which could be valuable in developing pharmacological strategies for the treatment of alcoholism and alcohol abuse.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA012262-01A1
Application #
6093655
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Egli, Mark
Project Start
2000-04-01
Project End
2005-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
1
Fiscal Year
2000
Total Cost
$285,969
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Psychiatry
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
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Ding, Zheng-Ming; Ingraham, Cynthia M; Rodd, Zachary A et al. (2016) Alcohol drinking increases the dopamine-stimulating effects of ethanol and reduces D2 auto-receptor and group II metabotropic glutamate receptor function within the posterior ventral tegmental area of alcohol preferring (P) rats. Neuropharmacology 109:41-48
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Toalston, Jamie E; Deehan Jr, Gerald A; Hauser, Sheketha R et al. (2014) Reinforcing properties and neurochemical response of ethanol within the posterior ventral tegmental area are enhanced in adulthood by periadolescent ethanol consumption. J Pharmacol Exp Ther 351:317-26
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
Wilden, Jessica A; Qing, Kurt Y; Hauser, Sheketha R et al. (2014) Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell. J Neurosurg 120:997-1005
Hauser, Sheketha R; Deehan Jr, Gerald A; Toalston, Jamie E et al. (2014) Enhanced alcohol-seeking behavior by nicotine in the posterior ventral tegmental area of female alcohol-preferring (P) rats: modulation by serotonin-3 and nicotinic cholinergic receptors. Psychopharmacology (Berl) 231:3745-55

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