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

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

Disclosures

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

In This Article

Discussion

How do we feel close and connected to our loved ones? The present study is the first to show that the opioid antagonist, naltrexone, reduces VS and MI activity to both social and physical warmth and erases the neural overlap between the two experiences. Together, these results advance two major theoretical perspectives on social bonding: (i) the brain opioid theory of social attachment and (ii) the notion that social and physical warmth share similar mechanisms. Each is elaborated on in turn.

Brain Opioid Theory of Social Attachment

The brain opioid theory of social attachment suggests that blocking opioid activity would subsequently alter social connection (Panksepp et al., 1980a; Panksepp, 1998). Consistent with some research findings on social behavior in animals, blocking opioids (vs placebo) in the current study reduced activity in the VS and MI to messages from participants' own close others. In addition, naltrexone erased the positive correlation between feelings of social connection toward messages from close others and neural activity that was present in the placebo group. These results are the first to show that naltrexone causes a disconnect between subjective feelings of social connection and neural activity to reading messages that affirm one is loved, cared for, known and appreciated by their own loved ones.

Although the drug effect on self-reported feelings of social connection to the social warmth task was in the expected direction, results did not reach statistical significance. In everyday life, meaningful messages from close others, like the ones presented in the current study, are rare. Therefore, any feelings of social connection experienced after reading such messages may not be reduced (at a statistically significant level) by a single drug administration. Indeed, in our previous work with naltrexone and the same social warmth task, naltrexone did not have an effect on feelings of social connection during the first presentation of messages (Inagaki et al., 2016a). Instead, the current results suggest that opioids may have a more nuanced effect on social connection experiences by not only altering neural responding but also disrupting the link between self-reported subjective experience and neural activity. Future work may wish to examine additional neurochemical contributors to self-reported feelings of social connection [e.g. oxytocin (Bartz, 2016), dopamine (Atzil et al., 2017)] and their interactions with opioids as they contribute to subjective social experience. However, taken together, the results on the effects of naltrexone to the social warmth task add to a growing literature to suggest that the central actions of opioids alter experiences of social connection in humans (Machin and Dunbar, 2011; Nummenmaa et al., 2015; Inagaki, 2018).

Social and Physical Warmth

The present research contributes additional data in support of the notion that social warmth and the feelings of connection that can result from interacting with our closest others may act on the same pathways as physical warmth. An emerging literature shows that physical warmth can cause increases in feelings of social connection and that feelings of social connection can likewise increase feelings of warmth (e.g. Inagaki and Eisenberger, 2013). Responses to social and physical warmth in the current study further suggest a link in two ways. First, holding a warm (vs cool) object increased feelings of social connection and VS and MI activity. That is, simply holding a warm object was sufficient to temporarily increase feelings of social connection and VS and MI activity. Second, neural responding to social and physical warmth showed overlapping activity in the VS and MI, regions previously associated with close social bonds (Bartels and Zeki, 2004; Aron et al., 2005; Acevedo et al., 2012; Inagaki and Eisenberger, 2013; Atzil et al., 2017).

Naltrexone, however, disrupted the neural patterns present in the placebo condition. First, naltrexone reduced VS and MI activity to physical warmth. Second, and perhaps more notable, naltrexone altered neural responding such that the overlap in responding to social and physical warmth that was present in the placebo group was eliminated. Together, these results suggest that another route by which opioids contribute to social bonding is via its effects on physical warmth.

Implications for Social Bonding and Relationship Maintenance

Close social relationships that one maintains over time are the most critical relationships to health and well-being (e.g. Agerbo et al., 2013). The current results have implications for understanding how opioids contribute to the maintenance of close social bonds. Specifically, results support the theory that opioids might affect thermoregulatory pathways [afferent central nervous system (CNS) pathways that bring the physiological condition of the body to the brain] and thus thermoregulation, the process by which the body maintains its temperature around a normotensive range, but not set point, or the level at which warm is considered warm (Adler et al., 1988; Panksepp, 1998). In the current study, the thermoregulatory pathways tested include the VS and MI and the action of naltrexone on these brain regions. It is important to highlight that additional research that directly measures thermoregulation and its correlates (e.g. core body temperature, fever and shivering) as they contribute to social connection is needed. However, consistent with our theoretical perspective, naltrexone left perceptions of how warm the stimuli were rated (i.e. thermal intensity) unaltered but instead affected the more subjective experience of warmth. A possibility that could be tested with additional research is that the subjective experience of social bonding (feelings of social connection) is maintained similarly to how the thermoregulatory system maintains core temperature around a set point. In other words, feelings of social connection may fluctuate around a normotensive range, with the endogenous opioid system assisting in this maintenance. There is at least one study suggestive of a relationship between thermoregulation and the maintenance of affective experience. A single dose of whole-body heating (vs sham procedure) in individuals suffering from depression produces improvements in depressive symptoms both 1 week and 6 weeks after treatment, suggesting a long-term effect (Janssen et al., 2016).

Also consistent with the notion that opioids contribute to the maintenance of close social bonds, naltrexone affected neural responses to messages from some of our participants' own close others (e.g. parents, friends, romantic partners). However, naltrexone did not alter similar neural responses to messages from strangers. In a similar vein, naltrexone altered neural responses to warm stimuli, which may signal the proximity of close others but not cool stimuli (for the ROI results only). We have previously shown that the effects of naltrexone can be separated from general pleasant responding to both social warmth (Inagaki et al., 2016a) and physical warmth (Inagaki et al., 2015). The current results further clarify the contribution of opioids to social connection to suggest that opioids alter neural activity toward close others and related stimuli that might signal the presence of close others but not toward those one is not close to. These results not only underscore the similarities between social and physical warmth but also highlight an unrecognized and understudied side effect of opioid antagonism, namely altered neural responses to one's own close others. If opioids affect VS and MI activity to one's own close others after a single experience with these individuals (i.e. the social warmth task in the current study), it is possible opioids affect experiences that underlie bonding over time. However, as noted above, additional research that examines the long-term effects of weeks or months of naltrexone treatment are needed to directly assess the effects of naltrexone on relationships with close others over time.

Some limitations warrant discussion. The effect of naltrexone on self-reported feelings of social connection to social and physical warmth resulted in a pattern consistent with hypotheses but was not statistically significant. Indeed, the effect of naltrexone on feelings of social connection shows mixed results with some studies showing a statistically significant reduction (Inagaki et al., 2015; Inagaki et al., 2016a), some showing no effect (Tarr et al., 2017) and some showing an effect only after considering moderators (Depue and Morrone-Strupinsky, 2005). Similarly, holding a warm vs a cool object did not increase VS and MI activity corrected at the whole brain in the placebo group. However, holding a warm object compared to a neutral, room temperature object increased VS and MI activity, in line with primary hypotheses and in a replication of our previous findings (Inagaki and Eisenberger, 2013). Additional research with larger samples and tighter control over the thermal stimulation may be needed to understand the effect of naltrexone on subjective social feelings toward close others and tease apart the brain's response to warmer vs cooler temperatures.

In conclusion, this is the first study to show that naltrexone, an opioid antagonist, disrupts experiences of social connection by reducing VS and MI activity to social and physical warmth. Further, the effect of naltrexone was specific to close others and warmth, as naltrexone did not alter neural responses to strangers or cool stimuli. Within its limitations, the results contribute to an understanding of opioids and social bonding via two converging theories: the brain opioid theory of social attachment and a social-physical warmth overlap.

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