It takes two: The interplay between dopamine and oxytocin in social behavior

Social behavior, in its broadest sense, refers to interactions between individuals of the same species, or conspecifics, and is essential for reproduction, resource sharing, and social organization. Affiliative behaviors help establish relationships, promote cooperation, and support group success, while aggressive behaviors serve protective or competitive purposes, aiding individual survival. In the neurobiology of social behavior, the neuropeptide oxytocin plays a central role. Initially known for its functions in childbirth and lactation, oxytocin is now recognized for its critical involvement in social behaviors like bonding, empathy, and caregiving (Froemke and Young, 2021). It helps regulate social interactions, emotional responses, and social cognition, making it an important neuromodulator in the formation and maintenance of social connections. Although some studies note that oxytocin may not always elicit prosocial effects depending on variable such as length of administration and context (Anpilov et al., 2020; Huang et al., 2014). Similarly, dopamine, a neurotransmitter linked to value tracking and learning, also plays a key role in social behaviors. It helps reinforce behaviors by signaling rewards and motivating social interactions, influencing both affiliative and competitive behaviors (Love, 2014). In their review, “Convergence of Oxytocin and Dopamine Signalling in Neuronal Circuits: Insights into the Neurobiology of Social Interactions Across Species,” Rappeneau and Castillo Díaz examine the literature on the interplay between these two neuromodulators and their significance in social behavior (Rappeneau and Castillo Díaz, 2024).

The review begins by exploring the basic biology of how oxytocin directly modulates the firing of dopamine neurons in the substantia nigra and ventral tegmental area (VTA). Several human studies are discussed, combining fMRI with intranasal oxytocin administration, showing task-specific changes in the activity of regions such as the amygdala, insula, orbitofrontal cortex, and nucleus accumbens (NAc)—areas known to receive dopaminergic projections. Additional fMRI research on social altruism and maternal behavior highlights increased activation in dopamine-innervated areas and a correlation between D2-receptor responses and synchronized maternal behavior, pointing to the collaboration between oxytocin and dopamine systems in facilitating social behavior. To address the lack of mechanistic and causal evidence in human studies, animal research is presented. One study using optogenetic activation of paraventricular nucleus (PVN) oxytocin-releasing terminals in the VTA demonstrates enhanced social place preference in mice, suggesting this pathway reinforces social interactions. Further studies emphasize the roles of both oxytocin and dopamine in pair bond formation in monogamous prairie voles. These findings help interpret human imaging data, although direct simultaneous measurement of dopamine and oxytocin has only recently become possible in animals through advances in genetically encoded biosensors (Qian et al., 2023).

Next, the review focuses on the role of oxytocin and dopamine system dysregulation in disorders characterized by social deficits, including posttraumatic stress disorder (PTSD), autism spectrum disorder (ASD), and schizophrenia. For PTSD, animal models such as adolescent social isolation and social defeat stress highlight alterations in these systems. Social isolation increases PVN-to-VTA activity, impairing social recognition in male mice, while social defeat stress elevates VTA dopamine neuron firing in mice and dopamine release in rats. Although these models underscore the involvement of oxytocin and dopamine in social stress, other models, such as fear conditioning, the pairing of a neutral cue to a noxious stimulus such as a foot shock, could provide additional insights. Furthermore, this noxious stimulus can be paired with a social cue in a model termed social fear conditioning, although this is more so considered a model of social anxiety disorder (Toth et al., 2012). In ASD, human imaging studies reveal complicated findings with oxytocin treatment. One study showed intranasal enhances social learning and correlates with increased NAc activity, but another study, focusing on social reward, failed to show a significant behavioral effect although they did see increased NAc activation in ASD patients. Animal studies, including Shank3B and Stx1a knockout (KO) mice, demonstrate that oxytocin can rescue social deficits and improve dopamine plasticity. For schizophrenia, evidence shows that oxytocin administration improves social behavior, though the interplay between oxytocin and dopamine remains underexplored.

Interestingly, the review does not address substance use disorder (SUD), despite the well-established connection between dopamine dysregulation and the development of SUD. Dopamine, plays a central role in the reinforcement of drug-seeking behavior and the maladaptive learning processes that underpin addiction (Koob and Volkow, 2016). Given the crucial role of dopamine in addiction, understanding how oxytocin may interact with this system in the context of SUD could provide valuable insights into new therapeutic approaches. Moreover, social factors have been shown to significantly influence the development and progression of SUD. Recent animal models have highlighted how social stressors, social isolation, and environmental factors can affect addiction behaviors, suggesting that the social context is integral to both the onset and recovery from substance use (Venniro et al., 2022). Indeed, since oxytocin is implicated in modulating social behaviors, including those related to stress, its role in substance use and recovery has been reviewed previously (Bowen and Neumann, 2017, 2018) and remains an important area of study. Exploring how the interplay between these systems might influence social aspects of addiction could lead to more effective interventions for individuals with SUD, especially considering that both oxytocin and dopamine are key players in social behavior and SUD.

Rappeneau and Castillo Díaz provide a thorough cross-species analysis of the interplay between the oxytocin and dopamine systems in social behavior. While oxytocin has been extensively studied in this context, further investigation is needed, particularly regarding its role in social disorders such as ASD, SUD, and schizophrenia. In contrast, dopamine’s involvement in social reward and learning is a more recent focus but is well-established in its connection to psychosocial disorders. Both neuromodulators influence a wide range of behaviors involving conspecifics, acting on numerous brain regions to regulate complex social interactions. This review effectively summarizes the current understanding in the field and highlights critical gaps for future research.