Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds

  1. Shanna L Resendez  Is a corresponding author
  2. Piper C Keyes
  3. Jeremy J Day
  4. Caely Hambro
  5. Curtis J Austin
  6. Francis K Maina
  7. Lori Eidson
  8. Kirsten A Porter-Stransky
  9. Natalie Nevárez
  10. J William McLean
  11. Morgan A Kuhnmuench
  12. Anne Z Murphy
  13. Tiffany A Mathews
  14. Brandon J Aragona  Is a corresponding author
  1. University of Michigan, United States
  2. University of Alabama at Birmingham, United States
  3. Wayne State University, United States
  4. Georgia State University, United States
  5. University of Michigan-Ann Arbor, United States

Abstract

Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds.

Article and author information

Author details

  1. Shanna L Resendez

    Neuroscience Graduate Program, University of Michigan, Ann Arbor, United States
    For correspondence
    shanna_resendez@med.unc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3831-5481
  2. Piper C Keyes

    Department of Psychology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jeremy J Day

    Department of Neurobiology, University of Alabama at Birmingham, Birmangham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Caely Hambro

    Department of Psychology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Curtis J Austin

    Department of Psychology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Francis K Maina

    Department of Chemistry, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Lori Eidson

    Neuroscience Institute, Georgia State University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kirsten A Porter-Stransky

    Department of Psychology, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Natalie Nevárez

    Department of Psychology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. J William McLean

    Department of Neurobiology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Morgan A Kuhnmuench

    Department of Psychology, University of Michigan-Ann Arbor, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Anne Z Murphy

    Neuroscience Institute, Georgia State University, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Tiffany A Mathews

    Department of Chemistry, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Brandon J Aragona

    Neuroscience Graduate Program, University of Michigan, Ann Arbor, United States
    For correspondence
    aragona@umich.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments in this study were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#5531) of the University of Michigan. Experiments conducted in this study were approved by the Institutional Biosafety Committee (#1331) at the University of Michigan. All surgery was performed under ketamine and xylazine anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Richard D Palmiter, Howard Hughes Medical Institute, University of Washington, United States

Publication history

  1. Received: February 22, 2016
  2. Accepted: July 1, 2016
  3. Accepted Manuscript published: July 2, 2016 (version 1)
  4. Version of Record published: August 3, 2016 (version 2)
  5. Version of Record updated: August 5, 2016 (version 3)

Copyright

© 2016, Resendez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,393
    Page views
  • 707
    Downloads
  • 40
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Shanna L Resendez
  2. Piper C Keyes
  3. Jeremy J Day
  4. Caely Hambro
  5. Curtis J Austin
  6. Francis K Maina
  7. Lori Eidson
  8. Kirsten A Porter-Stransky
  9. Natalie Nevárez
  10. J William McLean
  11. Morgan A Kuhnmuench
  12. Anne Z Murphy
  13. Tiffany A Mathews
  14. Brandon J Aragona
(2016)
Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds
eLife 5:e15325.
https://doi.org/10.7554/eLife.15325

Further reading

    1. Neuroscience
    Guy Avraham, Jordan A Taylor ... Samuel David McDougle
    Research Article

    Traditional associative learning tasks focus on the formation of associations between salient events and arbitrary stimuli that predict those events. This is exemplified in cerebellar-dependent delay eyeblink conditioning, where arbitrary cues such as a light or tone act as conditioning stimuli (CSs) that predict aversive sensations at the cornea (unconditioned stimulus, US). Here we ask if a similar framework could be applied to another type of cerebellar-dependent sensorimotor learning – sensorimotor adaptation. Models of sensorimotor adaptation posit that the introduction of an environmental perturbation results in an error signal that is used to update an internal model of a sensorimotor map for motor planning. Here we take a step towards an integrative account of these two forms of cerebellar-dependent learning, examining the relevance of core concepts from associative learning for sensorimotor adaptation. Using a visuomotor adaptation reaching task, we paired movement-related feedback (US) with neutral auditory or visual contextual cues that served as conditioning stimuli (CSs). Trial-by-trial changes in feedforward movement kinematics exhibited three key signatures of associative learning: Differential conditioning, sensitivity to the CS-US interval, and compound conditioning. Moreover, after compound conditioning, a robust negative correlation was observed between responses to the two elemental CSs of the compound (i.e., overshadowing), consistent with the additivity principle posited by theories of associative learning. The existence of associative learning effects in sensorimotor adaptation provides a proof-of-concept for linking cerebellar-dependent learning paradigms within a common theoretical framework.

    1. Neuroscience
    Yu-Chi Chen, Aurina Arnatkevičiūtė ... Kevin M Aquino
    Research Article

    Asymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (~65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences.