Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders

Abstract

Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a potential therapeutic target to improve mood and socio-affiliative behaviors in patients with profound social deficits and/or drug addiction.

Figure 1

Major dopamine pathways in the rat brain. The nigrostriatal pathways are comprised of dopamine cell bodies in the SN, from here dopamine fibers innervate several brain regions including the ST, PFC, NA, and AMG (light graey line). Mesocortical and mesolimbic dopamine pathways originate in the VTA and project to the PFC (dark gray line), and NA (black‐dotted line), respectively. The tuberoinfundibular dopamine system is comprised of dopamine fibers originating in the ARC and terminating in the ME (dark gray dotted line). Dopamine projections from the ZI to the MPOA, SON, and PVN of the hypothalamus comprise the incertohypothalamic dopamine pathway (black line). The diencephalospinal dopamine system originates in the hypothalamus and projects to the thoracolumbar spinal cord (black ‐hashed line). PFC, prefrontal cortex; NA, nucleus accumbens; ZI, zona incerta; MPOA, medial preoptic nucleus; PVN, paraventricular nucleus; SON, supraoptic nucleus; AMG, amygdala; ARC, arcuate nucleus; VTA, ventral tegmental area; ME, median eminence; ST, striatum; SC, spinal cord.

Figure 2

Major dopamine pathways and their relationship to oxytocin neuron populations. Basic framework of proposed interactions between dopamine and oxytocin in the rodent social brain. Sagittal view of a rat brain illustrating potential neural pathways involving dopamine and oxytocin during sociosexual behavior (proposed pathways underlying pair bonding were taken from prairie vole literature as rats do not form pair bonds). Sociosexual behavior is governed by oxytocin release from the hypothalamic nuclei, namely, MPOA, SON, and PVN which receive dopaminergic innervation originating in the ZI. The hypothalamus exerts its pro‐social effects using oxytocin via (1) magnocellular oxytocin dendritic release which inturn diffuses throughtout the hypothalamus and to other sites and (2) via PVN extra‐hypothalamic oxytocin projections to the hippocampus, amygdala, VTA, and spinal cord where they have a role in sexual behavior, reward and pair bonding. During mating oxytocin release in the AMG, HC, and VTA facilitates social learning and memory and stimulates mesolimbic dopaminergic reward pathways projecting to the NA and PFC. Mating encourages pair bonding possibly via oxytocin release (likely to be supplied by the PVN) in the PFC and the NA, (or in the case of males, vasopressin release in the ventral pallidium, not shown). PFC dopamine levels may increase upon oxytocinergic stimulation leading to further dopamine release in the NA via glutamatergic projections. Concurrently, NA dopamine may also be directly activated by oxytocin to modulate pair bonding. NA, nucleus accumbens; ZI, zona incerta; MPOA, medial preoptic nucleus; PVN, paraventricular nucleus; SON, supraoptic nucleus; AMG, amygdala; VTA, ventral tegmental area; HC, hippocampus; PFC, prefrontal cortex; OB, olfatory bulbs; SC, spinal cord.

Figure 3

Dopamine and oxytocin interactions during penile erection. Sagittal view of a rat brain illustrating proposed interactions between dopamine and oxytocin in the rodent brain during penile erection. During sexual arousal oxytocin acts in the AMG, HC, and VTA via parvocellular oxytocin projections and magnocellular oxytocin diffusion to stimulate the mesolimbic dopamine pathways originating in the VTA and projecting to the NA, which mediate sexual motivation and reward. Concurrently, meslimbic dopamine activates (via an unkown pathway) the incertohypothalamic doapmine system to stimulate oxytocinergic neurons in the PVN which then project to the SC and facilitate penile erection. The role of oxytocin action in the MPOA and SON during penile erection remains unknown, however, they may be involved in mediating those sexual events occurring after erection such as pelvic thrusting and/or ejaculation. OT, oxytocin; NA, nucleus accumbens; ZI, zona incerta; MPOA, medial preoptic nucleus; PVN, paraventricular nucleus; SON, supraoptic nucleus; AMG, amygdala; VTA, ventral tegmental area; HC, hippocampus; OB, olfatory bulbs; SC, spinal cord.

Figure 4

Summary of dopamine and oxytocin involvement in social behavior and behavioral disorders. Summary of potential dopamine and oxytocin interactions underlying socio‐affiliative behaviors and subsequent behavioral disorders. Central oxytocin neurons activated by incertohypothalamic (ZI) dopamine input and mesolimbic dopamine pathways driven by hypothalamic and limbic oxytocin release comprise part of the neural circuitry governing social behaviors. Disruptions or changes in these neurochemical pathways may partly underpin pathophysiologic mechanisms contributing to organic functions such as erectile dysfunction, but also adversely affect an array of social parameters, which can lead to the development of profound behavioral disorders. NA, nucleus accumbens; ZI, MPOA, medial preoptic nucleus; PVN, paraventricular nucleus; SON, supraoptic nucleus; AMG, amygdala; VTA, ventral tegmental area; HC, hippocampus; OB, olfatory bulbs; CP, caudate putamen; PFC, prefrontal cortex.