EXCEED THE SPACE PROVIDED. The long-range goals of this proposal are to better understand the neurobiological mechanismsun- derlying alcohol relapse in individuals at risk for alcoholism.The goals of the present application are to ex- amine neuronal alterations associated with a long-term 'Alcohol Deprivation Effect' (ADE) in rat lines selec- tively bred for high alcohol-seeking characteristics. The overall hypothesis to be tested is that, following chronic ethanol (E) drinking and extended abstinence, neuroadaptations develop and persist in key limbic regions of individuals at risk for alcoholism, which underlie alcohol relapse and contribute to theappear- ance of the ADE. This hypothesis will be tested in the selectively bred alcohol-preferring P and high alco- hol-drinking HAD lines of rats. After a single deprivation period, P rats show a robust ADE, which can be prolonged with repeated deprivations, whereas the HAD lines do not show a robust ADE until afterrepeat- ed deprivations.
The specific aims are designed to examine CMSchangeswhich are produced after chronic E drinking, and following single and repeated long-term deprivations.
Specific aim 1 will usethe intracranial self-administration technique to determine the dose-response effects for self-infusions of E into the post- erior VTA of P and HADrats to examine changes in the reinforcing properties ofE after one or more depri- vations.
Specific aim 2 will use the no-net-flux microdialysis procedure to determine changes in basal dopa- mine (DA) and serotonin (5-HT) neurotransmission in the nucleus accumbens (ACB) after long-term depri- vations. In vivo microdialysis will be used in specific aim 3 to determine changes in the functional activity of 5-HT3 receptors in the ACB of P and HAD rats after long-term deprivations.
Specific aim 4 will use the con- ditioned taste aversion test to determine changes in the threshold to the aversive effects of E after single and repeated deprivations. The results of this application will provide important information on neuralmech- anisms underlying the ADE and neuroadaptationsthat develop following single and multiple long-term deprivations, which contribute to alcohol relapse in individuals at risk for alcoholism. Such information will be importantfor developing pharmacotherapies for the prevention of alcohol relapse. PERFORMANCE SITE ========================================Section End===========================================

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
Project #
Application #
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Egli, Mark
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
Zip Code
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

Showing the most recent 10 out of 24 publications