Social affiliations play an important role in the onset and relapse of alcoholism and heavy drinking, yet this aspect of alcoholism and alcohol abuse has not been successfully modeled in rodents. Recently we developed the use of prairie voles (Microtus ochrogaster) to study negative (facilitating) and positive (inhibitory) social influences on alcohol consumption. Specifically, we demonstrated alcohol preference and heavy ethanol intake in this species, and showed that pair-housed prairie voles influence each other's drinking. When voles are introduced to alcohol in pairs they exhibit higher alcohol preference than when they are introduced to alcohol being single-housed. In these pairs, one vole influences (i.e., increases) alcohol consumption of its partner - modeling facilitating influences on alcohol drinking. In contrast, during pairing of high- and low-drinking voles that have previously experienced alcohol when they were single- housed, the vole with higher basal intake tends to decrease its drinking thereby matching its partner - modeling inhibitory social influences. Thus, the prairie vole could serve as the first rodent model of the effects of specific inter-personal affiliations on high alcohol drinking in both directions. We hypothesize that prairie voles influence their partner's rate of alcohol consumption via acoustic communication as do humans and that this influence is regulated by dominant/submissive relations, the opiate and the vasopressin (AVP) systems. We propose to test this hypothesis through following four Specific Aims.
Specific Aim 1 : To test whether the social influences on alcohol drinking occur by synchronizing alcohol drinking and are influenced by dominant-submissive interactions.
Specific Aim 2 : To test the whether USVs contribute to coordinated drinking in voles further increasing the validity of our model.
Specific Aim 3 : To test whether the efficacy of an established pharmacotherapy of alcoholism targeting the endogenous opiate system is modulated by social influences.
Specific Aim 4 : To test whether the AVP system known to regulate social affiliations in prairie voles contributes to regulation of coordinated drinking. Taken together this work will for the first time reveal information on the biological mechanisms regulating social influence on excessive alcohol drinking in a rodent model.

Public Health Relevance

Social affiliations play a substantial role in the onset and relapse of alcoholism and heavy drinking, yet the mechanisms of this aspect of alcoholism are poorly understood. In this application we will use the prairie vole as a rodent model to study the mechanisms underlying effects of specific social affiliations on excessive alcohol use. The success of these studies may provide new insights into strategies for therapeutic treatments of alcoholism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA019793-02
Application #
8260839
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Egli, Mark
Project Start
2011-05-01
Project End
2016-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
2
Fiscal Year
2012
Total Cost
$277,200
Indirect Cost
$97,200
Name
Oregon Health and Science University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Walcott, Andre T; Smith, Monique L; Loftis, Jennifer M et al. (2018) Social transfer of alcohol withdrawal-induced hyperalgesia in female prairie voles. Soc Neurosci 13:710-717
Panksepp, J B; Rodriguez, E D; Ryabinin, A E (2017) Sweetened ethanol drinking during social isolation: enhanced intake, resistance to genetic heterogeneity and the emergence of a distinctive drinking pattern in adolescent mice. Genes Brain Behav 16:369-383
Giardino, W J; Rodriguez, E D; Smith, M L et al. (2017) Control of chronic excessive alcohol drinking by genetic manipulation of the Edinger-Westphal nucleus urocortin-1 neuropeptide system. Transl Psychiatry 7:e1021
Ryabinin, Andrey E; Giardino, William J (2017) Contribution of Urocortin to the Development of Excessive Drinking. Int Rev Neurobiol 136:275-291
Walcott, Andre T; Ryabinin, Andrey E (2017) Alcohol's Effects on Pair-Bond Maintenance in Male Prairie Voles. Front Psychiatry 8:226
Ryabinin, A E; Hostetler, C M (2016) Prairie Voles as a Model to Screen Medications for the Treatment of Alcoholism and Addictions. Int Rev Neurobiol 126:403-21
Hostetler, Caroline M; Phillips, Tamara J; Ryabinin, Andrey E (2016) Methamphetamine Consumption Inhibits Pair Bonding and Hypothalamic Oxytocin in Prairie Voles. PLoS One 11:e0158178
Smith, M L; Li, J; Cote, D M et al. (2016) Effects of isoflurane and ethanol administration on c-Fos immunoreactivity in mice. Neuroscience 316:337-43
Kaplan, Joshua S; Mohr, Claudia; Hostetler, Caroline M et al. (2016) Alcohol Suppresses Tonic GABAA Receptor Currents in Cerebellar Granule Cells in the Prairie Vole: A Neural Signature of High-Alcohol-Consuming Genotypes. Alcohol Clin Exp Res 40:1617-26
Anacker, Allison M J; Smith, Monique L; Ryabinin, Andrey E (2014) Establishment of stable dominance interactions in prairie vole peers: relationships with alcohol drinking and activation of the paraventricular nucleus of the hypothalamus. Soc Neurosci 9:484-94

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