Combinatorial Oxytocin Neuropharmacology in Social Cognition

Fan, Siqi; Weinberg-Wolf, Hannah; Piva, Matthew; Monte, Olga Dal; Chang, Steve

doi:10.1016/j.tics.2019.10.004

Cited by 15 publications

(15 citation statements)

References 12 publications

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Section: Discussionmentioning

confidence: 95%

“…Most other interventions had no effect on retention; while antidepressants, anticonvulsants, and disulfiram worsened retention compared to placebo ( 1 ). Conversely, intranasal oxytocin and naltrexone, a μ-opioid antagonist, may act synergistically to improve retention ( 46 – 48 ), and the combination warrants further investigation. Because retention in addiction treatment has generally been associated with improved long-term treatment outcomes, and there is a scarcity of available interventions to effectively address critically high dropout rates among stimulant users, further research into oxytocin's potential to improve treatment engagement is warranted.…”

Section: Discussionmentioning

confidence: 99%

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Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

et al. 2022

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The increasing prevalence of illicit stimulant use among those in opioid treatment programs poses a significant risk to public health, stimulant users have the lowest rate of retention and poorest outcomes among those in addiction treatment, and current treatment options are limited. Oxytocin administration has shown promise in reducing addiction-related behavior and enhancing salience to social cues. We conducted a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin administered twice daily for 6 weeks to male Veterans with stimulant use disorder who were also receiving opioid agonist therapy and counseling (n = 42). There was no significant effect of oxytocin on stimulant use, stimulant craving, or therapeutic alliance over 6 weeks. However, participants receiving oxytocin (vs. placebo) attended significantly more daily opioid agonist therapy dispensing visits. This replicated previous work suggesting that oxytocin may enhance treatment engagement among individuals with stimulant and opioid use disorders, which would address a significant barrier to effective care.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

et al. 2022

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“…Despite these impressive results, the importance of a combinatorial perspective in understanding neuromodulation remains underrepresented in the literature. This review will specifically highlight interactions between oxytocin and opioidergic circuits [82]. Existing reviews have done an excellent job summarizing known behavioural effects of oxytocin [43,48,50,52,58,71,82,83], the neural mechanisms underlying these effects [15][16][17]84,85] and potential hypotheses about the role of oxytocin in the brain and social behaviour [20,22,24].…”

Section: Introductionmentioning

confidence: 99%

Interplay between the oxytocin and opioid systems in regulating social behaviour

Putnam

Chang

2022

Phil. Trans. R. Soc. B

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The influence of neuromodulators on brain activity and behaviour is undeniably profound, yet our knowledge of the underlying mechanisms, or ability to reliably reproduce effects across varying conditions, is still lacking. Oxytocin, a hormone that acts as a neuromodulator in the brain, is an example of this quandary; it powerfully shapes behaviours across nearly all mammalian species, yet when manipulated exogenously can produce unreliable or sometimes unexpected behavioural results across varying contexts. While current research is rapidly expanding our understanding of oxytocin, interactions between oxytocin and other neuromodulatory systems remain underappreciated in the current literature. This review highlights interactions between oxytocin and the opioid system that serve to influence social behaviour and proposes a parallel-mechanism hypothesis to explain the supralinear effects of combinatorial neuropharmacological approaches. This article is part of the theme issue ‘Interplays between oxytocin and other neuromodulators in shaping complex social behaviours’.

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“…On the other hand, individuals with WS, a rare genetic disorder associated with hyper-sociality, exhibit heightened social engagement, increased attention to faces, and uninhibited approach to strangers (Barak and Feng, 2016). Central serotonergic functions are suspected to be dysregulated in both ASD and WS (August and Realmuto, 1989; Williams et al, 2011; Barak and Feng, 2016; Muller et al, 2016; Fan et al, 2020; Lew et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Increasing central serotonin with 5-HTP disrupts the inhibition of social gaze in non-human primates

Weinberg-Wolf

Fagan

Monte

et al. 2021

Preprint

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To competently navigate the world, individuals must flexibly balance distinct aspects of social gaze, orienting toward others and inhibiting orienting responses, depending on the context. These behaviors are often disrupted in patient populations treated with serotonergic drugs. However, the field lacks a clear understanding of how the serotonergic system mediates social orienting and inhibiting behaviors. Here, we tested how increasing central concentrations of serotonin with the direct precursor 5-Hydroxytryptophan (5-HTP) would modulate the ability of rhesus macaques to use eye movements to flexibly orient to, or inhibit orienting to, faces. Systemic administrations of 5-HTP effectively increased central serotonin levels and impaired flexible orientation and inhibition. Critically, 5-HTP selectively impaired the ability of monkeys to inhibit orienting to face images, whereas it similarly impaired orienting to face and control images. 5-HTP also caused monkeys to perseverate on their gaze responses, making them worse at flexibly switching between orientating and inhibiting behaviors. Furthermore, the effects of 5-HTP on performance correlated with a constriction of the pupil, an increased time to initiate trials, and an increased reaction time, suggesting that the disruptive effects of 5-HTP on social gaze behaviors are likely driven by a downregulation of arousal and motivational states. Taken together, these findings provide causal evidence for a modulatory relationship between 5-HTP and social gaze behaviors in non-human primates and offer translational insights for the role of the serotonergic system in social gaze.

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Combinatorial Oxytocin Neuropharmacology in Social Cognition

Cited by 15 publications

References 12 publications

Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

Intranasal Oxytocin for Stimulant Use Disorder Among Male Veterans Enrolled in an Opioid Treatment Program: A Randomized Controlled Trial

Interplay between the oxytocin and opioid systems in regulating social behaviour

Increasing central serotonin with 5-HTP disrupts the inhibition of social gaze in non-human primates

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