The dual role of dopamine in the modulation of information processing in the prefrontal cortex underlying social behavior

Abstract

Dopamine in the prefrontal cortex is essential for the regulation of social behavior. However, stress‐causing social withdrawal also promotes dopamine release in the prefrontal cortex. Thus, this evidence suggests opposite functions of dopamine in the prefrontal cortex. However, the influence of dopamine on prefrontal functions is yet to be fully understood. Here, we show that dopamine differentially modulated the neuronal activity triggered by social stimuli in the prefrontal cortex, depending on the duration of the dopamine activation (transient or sustained activation). Using chemogenetic techniques, we have found that social behavior was negatively regulated by a sustained increase in dopamine neuronal activity in the ventral tegmental area, while it was positively regulated by an acute increase. The duration of social interactions was positively correlated with the transient dopamine release triggered by social stimuli in the prefrontal cortex and negatively correlated with the sustained increase in prefrontal dopamine levels. Furthermore, the elevation of neural calcium signal, triggered by social stimuli, in the prefrontal cortex was attenuated by the persistent elevation of prefrontal dopamine levels, whereas an acute increase in dopamine levels enhanced it. Additionally, the chronic excess of dopamine suppressed c‐Fos induction triggered by social stimuli in prefrontal neurons expressing dopamine D1 receptors, but not D2 receptors. These results suggest that sustained activation of prefrontal dopamine, at the opposite of its transient activation, can reduce prefrontal activity associated with social behavior, even for identical dopamine concentrations. Thus, dopamine plays opposite roles in modulating prefrontal activity depending on the duration of its action.

Putative neural mechanisms underlying release‐mode‐specific abnormalities in dopamine neural activity in a schizophrenia‐like model: The distinct roles of glutamate and serotonin in the impaired regulation of dopamine neurons

“…It is believed that dopamine neural activity in the resting state results in sustained dopamine release (tonic release) (Grace, 1991). In agreement, I have previously shown that alterations of the mean firing rate of VTA dopamine neurons (under anaesthetized conditions) by chemogenetics are consistent with changes in dopamine levels in the prefrontal cortices of awake EGF‐treated rats and normal rats in the resting state (Sotoyama et al, 2021, 2022). On the other hand, I reported previously that there was no significant difference in the spike within the burst (SWB), which is a burst firing index, of VTA dopamine neurons between controls and EGF‐treated rats under anaesthetized conditions (Sotoyama et al, 2021).…”

“…For the chronic treatment, the CNO solution was filled in a mini‐osmotic pump (Alzet model 2002, Durect Co., CA, USA), and then the mini‐osmotic pump was implanted under the skin. The dose of CNO was determined according to our previous study (Sotoyama et al, 2022).…”

“…The index for social interaction of rats was measured according to a previous study (Sotoyama et al, 2022). A test rat (12-16 weeks old) was placed in the open-field box (45 cm in length  45 cm in width  30 cm in height, MED Associates) under a moderate light level (200 lx).…”

“…However, information on these dopaminergic abnormalities still remains controversial with often contradictory findings (Didriksen et al, 2017; Jentsch et al, 1997; Takahashi et al, 2019; Winter et al, 2009). Against this issue, it has been reported that continuously sustained dopamine level and a transiently fluctuating dopamine level exert opposite effects on information processing in the prefrontal cortex even under an identical concentration of dopamine, implying that actual dopamine signal cannot be determined simply by evaluation of extracellular dopamine levels without consideration of dopamine dynamics (Sotoyama et al, 2022). Nevertheless, previous pathophysiological studies of psychiatric disorders have not argued this dual role of dopamine between transient and sustained releases with sufficient discussion.…”

Social environment as a modulator of immunosenescence

“…This serotoninergic duality in social sensitivity seems to occur in concert with other neurochemical systems, such as the opioid system ( Refs 197,198). Similarly, other studies have pointed out the importance of dopaminergic pathways in social support/positive social environments, which state that the level of dopaminergic system activity could influence social support via the capacity of cognitive function ( Refs 199,200). Nonetheless, further research trying to decipher the role of each neural pathway on the effects of social support/positive social environments, especially in the context of immunosenescence, should be addressed.…”