Naltrexone Alters Responses to Social and Physical Warmth: Implications for Social Bonding

Tristen K. Inagaki; Laura I. Hazlett; Carmen Andreescu


Soc Cogn Affect Neurosci. 2019;14(5):471-479. 

In This Article

Opioids and Social Connection

Due to the importance of social connection for well-being, basic homeostatic mechanisms that maintain individuals at an optimal level of functioning may be involved in the maintenance of social bonds (Panksepp et al., 1980a; Panksepp, 1998). One candidate system that has received increasing attention in recent years is the endogenous opioid system, best known for its role in pain relief and pleasure (Leknes and Tracey, 2008). According to the brain opioid theory of social attachment, opioids contribute to emotional responding within close relationships and to the behavior or feelings that might promote further bonding (Panksepp et al., 1980a; Machin and Dunbar, 2011; Inagaki, 2018). Evidence for the theory comes primarily from animal research, which has shown that pharmacologic manipulations of the opioid system alter social-bonding behavior [reviewed in Machin and Dunbar (2011) and Loseth et al. (2014)]. For instance, blocking endogenous opioid activity (vs placebo; Panksepp et al., 1980b; Shayit et al., 2003) or using genetic knockout models (Moles et al., 2004) reduced social-bonding behavior. Conversely, naltrexone (vs placebo) has also been shown to increase social-bonding behavior (e.g. Martel et al., 1993; Schino and Troisi, 1992). Thus, animal research shows that opioids affect social behavior, suggesting opioids may also have implications for the affective experience of social connection in humans.

The relatively smaller human literature on opioids and social bonding also suggests opioids alter the affective experience related to social bonding (Inagaki, 2018). Naltrexone (vs placebo) reduced affiliative feelings to lab tasks designed to promote feelings of social connection to close others (Inagaki et al., 2015, 2016a) and more general affiliative stimuli of strangers (Depue and Morrone-Strupinsky, 2005; Schweiger et al., 2013; Chelnokova et al., 2014). Outside of the lab, daily feelings of social connection are also reduced by naltrexone (vs placebo; Inagaki et al., 2016a).

Opioids are theorized to contribute to social bonding via the system's actions on distinct brain regions. Indeed, the first indirect evidence for opioids and social bonding came from observations that the neural regions most densely concentrated in opioid receptors (Cross et al., 1987; Zubieta et al., 2001) are also the regions that contribute to social bonding. These regions include the ventral striatum (VS), middle insula (MI), ventral tegmental area (VTA), anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC; Bartels and Zeki, 2004; Aron et al., 2005; Acevedo et al., 2012; Inagaki and Eisenberger, 2013; Atzil et al., 2017). Positron emission tomography (PET) imaging, which examines opioid activity in vivo, confirmed initial observational evidence. Endogenous opioid release in males (i.e. decreased binding of the μ-opioid-specific ligand [11C]carfentanil) increased in the insula and cingulate cortices after a laughter manipulation with friends (Manninen et al., 2017). In addition, greater laughter between friends was associated with opioid-receptor binding in the VS, OFC, anterior and middle cingulate cortices at baseline. Similarly, increased desire for social interaction was associated with left VS binding to learning that one is liked by an opposite-sex stranger (Hsu et al., 2013). Collectively, results from animals and humans point to the opioid system as a promising contributor to social bonding.