Endogenous opioids facilitate intrinsically-rewarded birdsong

Abstract

Many songbirds sing in non-reproductive contexts while in flocks. Singing in such gregarious contexts is critical for maintaining and learning songs; however, song is not directed towards other individuals and has no obvious, immediate social consequences. Studies using conditioned place preference (CPP) tests of reward indicate that song production in gregarious contexts correlates positively with a bird’s intrinsic reward state and with opioid markers in the medial preoptic nucleus (mPOA). However, the causal involvement of opioids in gregarious song is unknown. Here we report that the selective mu opioid receptor (MOR) agonist fentanyl dose-dependently facilitates gregarious song and reduces stress/anxiety-related behavior in male and female European starlings. Furthermore, infusion of siRNA targeting MORs specifically in mPOA both suppresses gregarious song and disrupts the positive association between affective state and singing behavior, as revealed using CPP tests of song-associated reward. Results strongly implicate opioids in gregarious song and suggest that endogenous opioids in the mPOA may facilitate song by influencing an individual’s intrinsic reward state.

μ-Opioid Receptor Stimulation in the Nucleus Accumbens Increases Vocal–Social Interactions in Flocking European Starlings,Sturnus Vulgaris

“…Additionally, gregarious singing behavior is associated with opioid-mediated analgesia (Kelm-Nelson et al, 2012). These findings together suggest that opioids released in association with social interactions may act at MORs to promote social cohesion, by inducing reward and reducing the pain of being alone (Kelm-Nelson et al, 2012;Riters and Stevenson, 2012;Riters et al, 2014;Hahn et al, 2017;Stevenson et al, 2020).…”

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

“…Further to these reports across mammals, opioids are even reported to mediate certain types of singing in songbirds. For instance, fentanyl injections increased non-communicative, intrinsically rewarding singing in starlings [112].…”

The neurochemistry of social reward during development: What have we learned from rodent models?

“…Furthermore, infusion of short interfering RNA (siRNA) targeting μ opioid receptors specifically in the mPOA both suppressed gregarious song and disrupted the positive association between affective state and singing behavior, as revealed using CPP tests of song-associated reward. These results suggest that song is reinforced extrinsically by the behavioral responses of conspecifics and that endogenous opioids in the mPOA may facilitate song in birds by influencing their rewarding state when in flocks (Stevenson et al 2020). On the same line, a recent study has pointed out the implication of opioid signaling in the mPOA in social play in rats (PNDs 35-39 at the time of testing): Thus, social play induced robust immediate early gene Egr1 expression in this brain region and increased cells expressing μ opioid receptors in the mPOA, thus supporting the hypothesis that the mPOA is part of a conserved neural circuit across vertebrates in which opioids act to govern affiliative, intrinsically rewarded social behaviors (Zhao et al 2020).…”