In cases of depression, anxiety, and autism spectrum disorders, social interactions that are typically rewarding can be aversive. Deficits can also be context-specific. For example, some individuals with autism are able to make directed requests (e.g., for food) that can be extrinsically reinforced (e.g., by receipt of food) but exhibit profound deficits in affiliative communication (e.g., nonsexual, chitchat) that promotes social bonds and is rewarding but does not result in an immediate, obvious extrinsic reinforcer. Many studies identify roles for dopamine and opioids in motivation and reward involved in directed, extrinsically-rewarded behaviors (e.g., food-, mate- or drug-directed); however, these mechanisms appear to differ from those underlying affiliative communication, leaving a critical gap in basic knowledge about intrinsic reward mechanisms underlying affiliative social behaviors. The objectives of this proposal are to identify mechanisms by which opioids act in the medial preoptic nucleus (mPOA) and nucleus accumbens (NAc) to initiate, maintain, and reward affiliative communication using the unique communication properties of a songbird experimental system. Neural systems underlying important behaviors are usually highly conserved across species, thus studies in songbirds are expected to uncover a core, conserved circuit in which opioids act to initiate, reward, and maintain important social behaviors in contexts for which there is no obvious extrinsic reward, across vertebrates. The central hypothesis is that opioids act at mu opioid receptors (MOR) in the mPOA?VTA?NAc circuit to initiate, facilitate, and reward affiliative social behaviors. The rationale is the need for basic, mechanistic information on core social circuits that underlie behaviors disrupted by mental illness. Based on preliminary data, three specific aims are proposed: 1) Dissociate the functional roles of MOR in mPOA and NAc on affiliative singing behavior; 2) Determine effects of MOR gene knockdown in mPOA and NAc on affiliative song-associated reward; 3) Determine how environmental factors modulate affiliative song via MOR.
In Aim 1 dual-cannula microinfusions of MOR agonists and antagonists into mPOA and NAc will be used to identify distinct roles played by MOR in mPOA and NAc in initiating and maintaining affiliative singing behavior.
In Aim 2 siRNA targeting MOR in mPOA and NAc will be used to examine the role of MOR in song-associated reward measured using conditioned place preference tests.
In Aim 3 environmental and site-specific pharmacological manipulations will be used to examine the impact of environmental stressors on MOR modulation of affiliative song. The approach is innovative because it advances the understanding of intrinsically-rewarded social behavior in songbirds with the goal of identifying core affiliative circuits. The proposal is significant because it will elucidate the role of MOR and reward in non-sexual, affiliative social behaviors and provide insight into core neural circuits that may be disrupted by mental illness in humans.

Public Health Relevance

The proposed research is relevant to public health because it will fill a gap in knowledge about neuromodulators and brain regions involved in affiliative, intrinsically-rewarded social communication, a type of communication that is disrupted in multiple mental health disorders. This project is relevant to NIMH?s mission, as knowledge about basic mechanisms underlying this type of communication is crucial to develop treatments that can restore the positive, affiliative social interactions that are devastated by mental illness.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Breeden, Andrew Lee
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University of Wisconsin Madison
Schools of Arts and Sciences
United States
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