Humans often consume alcoholic beverages to promote social interactions. On the other hand, alcohol abuse can have devastating effects on long-term social attachments. The mechanisms alcohol's effects on social relationships have been difficult to address. The situation changed with studies showing that many features of social bonding can be modeled using socially monogamous prairie voles (Microtus ochrogaster). Mechanisms regulating pair bonding in voles have later been shown to contribute to human social bonding, indicating strong construct validity of this animal model. We have initiated studies analyzing effects of social environment on alcohol consumption and, more recently, identified striking sex-dependent effects of voluntary alcohol consumption on the formation of male-female bonds in prairie voles. Specifically, voluntary alcohol consumption inhibited formation of partner preference in male animals, but facilitated partner preference in females. These findings indicated that alcohol acts through biological mechanisms to produce specific effects on adult social attachments. In parallel we found that alcohol drinking during cohabitation also produces sex-specific effects on c-Fos expression in the centrally-projecting Edinger-Westphal nucleus (EWcp). This application proposes to test whether EWcp contributes to alcohol's effects on pair bonding and further investigate alcohol's effects on pair bonding in three Specific Aims (SAs). In SA1 we will use CLARITY-based and standard immunohistochemistry to measure levels of several peptides and c-Fos across different brain regions during cohabitation in the presence or absence of alcohol. In SA2 we will test the causal role of EWcp activation in alcohol's effects on partner preference using the Designer Receptor(s) Exclusively Activated by Designer Drug(s) approach. Subsequent studies will test the roles of specific subpopulations of EWcp or brain regions identified in SA1. Finally, while our previous studies found effects of the first day of voluntary alcohol drinking on formation of pair-bonds, in SA3 we will test alcohol's effects on pair bonding following prolonged alcohol use and alcohol's effects on already established pair bonds.

Public Health Relevance

Alcohol abuse and dependence have a tremendous impact on social relationships. Understanding mechanisms regulating alcohol's effects on social relationships would greatly benefit recovering alcoholics, their families, and society. The proposed studies will for the first time investigate biological mechanisms by which alcohol affects social bonds.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA019793-06A1
Application #
9236886
Study Section
Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
Program Officer
Egli, Mark
Project Start
2011-05-01
Project End
2022-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
6
Fiscal Year
2017
Total Cost
$341,004
Indirect Cost
$116,004
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
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
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
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
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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
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
Anacker, Allison M J; Ahern, Todd H; Hostetler, Caroline M et al. (2014) Drinking alcohol has sex-dependent effects on pair bond formation in prairie voles. Proc Natl Acad Sci U S A 111:6052-7
Hostetler, Caroline M; Ryabinin, Andrey E (2014) Social partners prevent alcohol relapse behavior in prairie voles. Psychoneuroendocrinology 39:152-7

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