Abstract

The long-range goals of this proposal are to better understand the neurobiological mechanism involved in alcohol relapse. The goals of this application are to (a) better characterized the long-term """"""""Alcohol Deprivation Effect"""""""" (ADE) that develops in some experimental animals following prolonged (1 week or longer) alcohol abstinence and (b) determine if any neuroadaptive changes in certain monamine systems are associated with the ADE. The ADE is described as an enhanced intake of ethanol following a period of alcohol deprivation. The hypothesis to be tested is that, following chronic alcohol drinking and extended abstinence, long-term neuroadaptations, involving alterations in certain serotonin (5-HT) pathways, develop in individuals at risk for alcoholism, which maintain or enhance the rewarding effects of ethanol and contribute to the appearance of the ADE and alcohol relapse. This hypothesis will be tested using adult male alcohol-preferring P rats, which readily demonstrate an ADE following an alcohol deprivation period of one week or longer.
The specific aims will be designed to (1) further characterize the long-term ADE in the P line of rats and determine if a long-term ADE can be produced in the high alcohol-drinking HAD replicate lines of rats, as well as in non-selected Wistar rats; (2) examine whether alterations in the 5-HT3 receptor and/or 5-HT neurotransmission can be found after extended alcohol deprivation in the P rat; and (3) determine, using operant techniques (i.e., progressive-ratio, choice and extinction paradigms), if the reinforcing properties of ethanol are enhanced in the P rats following alcohol abstinence. The results of this proposal will provide information on the neural basis of the ADE. Furthermore, if the ADE observed in animals reflects some aspects of alcohol relapse in humans, then the findings from this application may provide some fundamental knowledge of possible neurobiological factors contributing to alcohol relapse.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA011261-01A1
Application #
2389935
Study Section
Special Emphasis Panel (ZRG4-ALTX-3 (01))
Project Start
1997-08-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

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

  Publications

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
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
Deehan Jr, Gerald A; Brodie, Mark S; Rodd, Zachary A (2013) What is in that drink: the biological actions of ethanol, acetaldehyde, and salsolinol. Curr Top Behav Neurosci 13:163-84
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
Franklin, Kelle M; Engleman, Eric A; Ingraham, Cynthia M et al. (2009) A single, moderate ethanol exposure alters extracellular dopamine levels and dopamine d receptor function in the nucleus accumbens of wistar rats. Alcohol Clin Exp Res 33:1721-30
Rodd, Zachary A; Bell, Richard L; Kuc, Kelly A et al. (2009) Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of high-alcohol-drinking (HAD) rats. Addict Biol 14:152-64
Toalston, Jamie E; Oster, Scott M; Kuc, Kelly A et al. (2008) Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats. Alcohol 42:277-84
Rodd, Zachary A; Gryszowka, Victoria E; Toalston, Jamie E et al. (2007) The reinforcing actions of a serotonin-3 receptor agonist within the ventral tegmental area: evidence for subregional and genetic differences and involvement of dopamine neurons. J Pharmacol Exp Ther 321:1003-12
Liu, Wen; Thielen, Richard J; Rodd, Zachary A et al. (2006) Activation of serotonin-3 receptors increases dopamine release within the ventral tegmental area of Wistar and alcohol-preferring (P) rats. Alcohol 40:167-76
Bell, Richard L; Rodd, Zachary A; Lumeng, Lawrence et al. (2006) The alcohol-preferring P rat and animal models of excessive alcohol drinking. Addict Biol 11:270-88

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