The broad, long-term goal of this project is to improve our understanding of the biological processes that contribute to the etiology and maintenance of excessive drinking and alcoholism in humans. The project focuses directly on variables influencing ethanol's hedonic (rewarding and aversive) effects. The central, organizing hypothesis of this. research is that. ethanol's hedonic effects are modulated by ethanol-induced hypothermia. Research completed during the previous project period has supported this hypothesis by showing that ethanol's aversive effects are weakened when ethanol hypothermia is reduced. The general experimental strategy proposed here involves examination of variables believed to influence ethanol's thermal and hedonic effects in three behavioral tasks using animals (rats, mice): taste conditioning, place conditioning, and operant oral self-administration of ethanol. Body temperature effects of ethanol will be monitored continuously using radio telemetry. Proposed experiments will address the central hypothesis from three directions. One series of experiments is intended to further characterize and extend our findings on temperature-dependent modulation of ethanol's hedonic effects. These experiments will examine effects of high and low ambient temperature, signalling stimuli , and rebound hyperthermia on ethanol hypothermia and behavioral measures of ethanol's positive and negative effects. A second series of experiments will address suggestions that effects of opiate agonists or antagonists on ethanol's hedonic properties are mediated by changes in ethanol hypothermia and that temperature-dependent alterations in ethanol's hedonic effects are mediated by changes in endogenous opioid activity. The first study in this series will parametrically examine effects of morphine and naloxone on ethanol hypothermia, while subsequent studies will examine ethanol-opioid system interactions in each of the behavioral tasks. The of experiments will study the genetic relationship between ethanol's thermal and hedonic effects using genetically heterogeneous mice, mice selectively-bred for sensitivity or resistance to ethanol hypothermia (HOT and COLD), as well as a panel of 15 inbred mouse strains. These studies will assess effects of altered ambient temperature on ethanol hypothermia and behavior in taste and place conditioning tasks. Overall, this research will further characterize the relationship between ethanol's thermal and hedonic effects and begin to shed light on possible neurochemical mechanisms. Positive findings would strongly encourage further study of the role played by ethanol's thermal effects in the etiology of excessive drinking and alcoholism. An important implication of this hypothesis is that individual differences in sensitivity to ethanol's thermal effects due either to genotype, experience, or environmental conditions may be critically involved in the development of excessive drinking and dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA007702-07
Application #
2044077
Study Section
Special Emphasis Panel (SRCA (51))
Project Start
1988-04-01
Project End
1998-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Psychology
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239
Cunningham, Christopher L; Shields, Chloe N (2018) Effects of multi-modal cues on conditioned place preference in C57BL/6J and DBA/2J mice. Psychopharmacology (Berl) 235:3535-3543
Cunningham, Christopher L; Shields, Chloe N (2018) Effects of sex on ethanol conditioned place preference, activity and variability in C57BL/6J and DBA/2J mice. Pharmacol Biochem Behav 173:84-89
Font, Laura; Houck, Christa A; Cunningham, Christopher L (2017) Naloxone effects on extinction of ethanol- and cocaine-induced conditioned place preference in mice. Psychopharmacology (Berl) 234:2747-2759
Pina, Melanie M; Cunningham, Christopher L (2017) Ethanol-seeking behavior is expressed directly through an extended amygdala to midbrain neural circuit. Neurobiol Learn Mem 137:83-91
Pina, Melanie M; Cunningham, Christopher L (2016) Involvement of ventral tegmental area ionotropic glutamate receptors in the expression of ethanol-induced conditioned place preference. Behav Brain Res 313:23-29
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
Pina, Melanie M; Young, Emily A; Ryabinin, Andrey E et al. (2015) The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice. Neuropharmacology 99:627-38
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
Cunningham, Christopher L; Zerizef, Courtney L (2014) Effects of combining tactile with visual and spatial cues in conditioned place preference. Pharmacol Biochem Behav 124:443-50
Pina, Melanie M; Cunningham, Christopher L (2014) Effects of the novel cannabinoid CB1 receptor antagonist PF 514273 on the acquisition and expression of ethanol conditioned place preference. Alcohol 48:427-31

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