This project is directly concerned with the learning and motivational processes underlying ethanol-seeking behavior. The long-term goal is to improve our understanding of the behavioral and neurobiological process that contribute to the etiology, maintenance, elimination and relapse of alcoholism. The general experimental strategy involves study of ethanol's motivational effects in oral self-administration and place conditioning tasks using animals. Special emphasis will be placed on the learning that results from the predictive relationship between environmental stimuli and exposure to ethanol rewarding or aversive effects. The central organizing hypothesis of this research is that ethanol-predictive stimuli have a direct impact on ethanol's motivational effects and that they are importantly involved in motivating or directing ethanol-seeking behavior, including the phenomenon of relapse after extinction or abstinence. One set of proposed experiments will examine effects of ethanol-predictive stimuli on conditioned hyperthermia and barpressing in a signaled self-administration procedure using rats and mice. Variables of interest include: Sucrose concentration, CS-ethanol overlap, ethanol access duration and conditioned reinforcement. The second set of studies will determine effects of ethanol-predictive stimuli on conditioned place preference and aversion in rats and mice. Variables of interest include: dose, number of trials, CS-ethanol interval, genotype, and route of administration. The final series of experiments will study the role of ethanol-predictive stimuli in extinction, relapse and relapse prevention. In addition to improving our understanding of ethanol-predictive stimuli, these studies will shed new light on apparent species differences in ethanol s motivational effects, and on findings that ethanol-predictive stimuli can acquire opposing motivational effects within the same species. A better understanding of these issues is essential for using these animal models to study neurobiological and genetic contributions to alcoholism. This project should help focus future research on the neurobiological mechanisms of ethanol-seeking behavior, aid in the development of beneficial treatments for alcohol abuse, and facilitate identification of effective relapse prevention strategies. These studies could prove to be especially useful in the evaluation of putative pharmacotherapies intended to reduce alcohol craving and in the design of behavioral interventions to decrease ethanol-seeking behavior.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Egli, Mark
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Oregon Health and Science University
Other Basic Sciences
Schools of Medicine
United States
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Barkley-Levenson, Amanda M; Cunningham, Christopher L; Smitasin, Phoebe J et al. (2015) Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice. Addict Biol 20:80-90
Barkley-Levenson, Amanda M; Crabbe, John C (2015) Genotypic and sex differences in anxiety-like behavior and alcohol-induced anxiolysis in High Drinking in the Dark selected mice. Alcohol 49:29-36
Hitchcock, Leah N; Cunningham, Christopher L; Lattal, K Matthew (2014) Cue configuration effects in acquisition and extinction of a cocaine-induced place preference. Behav Neurosci 128:217-27
Pina, Melanie M; Cunningham, Christopher L (2014) Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice. Psychopharmacology (Berl) 231:459-68
Groblewski, Peter A; Cunningham, Christopher L (2012) Repeated microinjections into the medial prefrontal cortex (mPFC) impair extinction of conditioned place preference in mice. Behav Brain Res 230:299-303
Font, Laura; Cunningham, Christopher L (2012) Post-retrieval propranolol treatment does not modulate reconsolidation or extinction of ethanol-induced conditioned place preference. Pharmacol Biochem Behav 101:222-30
Groblewski, Peter A; Ryabinin, Andrey E; Cunningham, Christopher L (2012) Activation and role of the medial prefrontal cortex (mPFC) in extinction of ethanol-induced associative learning in mice. Neurobiol Learn Mem 97:37-46
Gremel, Christina M; Young, Emily A; Cunningham, Christopher L (2011) Blockade of opioid receptors in anterior cingulate cortex disrupts ethanol-seeking behavior in mice. Behav Brain Res 219:358-62
Giardino, William J; Cocking, Davelle L; Kaur, Simranjit et al. (2011) Urocortin-1 within the centrally-projecting Edinger-Westphal nucleus is critical for ethanol preference. PLoS One 6:e26997
Groblewski, Peter A; Franken, Frederick H; Cunningham, Christopher L (2011) Inhibition of extracellular signal-regulated kinase (ERK) activity with SL327 does not prevent acquisition, expression, and extinction of ethanol-seeking behavior in mice. Behav Brain Res 217:399-407

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