Avaliação do papel da neurotransmissão de ocitocina na modulação da ansiedade induzida em camundongos pelo modelo de empatia para dor

Abstract

The success of social interaction is a necessary factor for human survival and depends on the ability to understand and experience emotions that the other is feeling. Some studies observed an increase in anxiety in rodents living with a conspecific submitted to a stressful situation, which was analyzed as emotional contagion, that is, the dissemination of forms of emotion from one individual to another. Recent studies have shown that the cohabitation of mice in pairs with a conspecific submitted to neuropathic pain increases the nociceptive response in observers submitted to the abdominal writhing test and in anxiety indices in mice exposed to the elevated plus maze (EPM). Therefore, these studies show the social modulation of pain and anxiety. On the other hand, in autism-induced rodents, a decrease in prosocial behaviors and an increase in anxiety were observed compared to the control group. Using this model, it was observed that the administration of oxytocin produced an increase in prosocial behavior in mice. Given the above, considering that there are studies linking oxytocin to increased prosocial behaviors and anxiolytic effects in rodents and that rodents exposed to the empathy model for pain showed anxiety-related responses, this study aimed to investigate whether the antagonism of oxytocin receptors with atosiban may interfere with the increase in anxiety induced by living with a conspecific undergoing chronic pain. For this, male Swiss-albino mice were separated into pairs during a 28-day coexistence protocol. After 14 days of living together, one of the animals in the pair underwent surgery for sciatic nerve constriction (NC) or surgery without nerve constriction (Sham). On the 28th day, the animal that lived with its conspecific NC or Sham received an injection of vehicle or atosiban [0.25, 0.5 and 1.0 mg/kg, intraperitoneally], and after 30 minutes, it was submitted to the test in the EPM for five minutes. To confirm the contact with the animal with nociception, on the 29th day, the hot plate test was performed in both groups (NC and Sham). The results demonstrate that living with conspecifics in chronic pain produced hypernociception and increased anxiety-related responses in partners when submitted to the elevated plus-maze test. Systemic treatment with the three doses of atosiban produced an anxiogenic-like effect in mice that lived with conspecifics without pain (Sham) but did not reverse the increase in anxiety observed in mice that lived with conspecifics with pain (NC). We suggest that the animals that lived with a partner without pain (sham) may have normal oxytocin levels, due to the absence of the stressor stimulus, facilitating the production of the anxiogenic effect induced by atosiban. However, in animals that lived with a partner in pain (NCC), oxytocin levels were probably increased as a result of the stressor stimulus and, therefore, blocking these receptors with the antagonist was not able to reverse the anxiogenic-like effect induced by the model. This study contributed to demonstrating the involvement of oxytocinergic neurotransmission in the modulation of the emotional response induced by living with conspecifics with chronic pain and without pain in mice. However, further research will be needed to elucidate the action of oxytocin and its blockade with chronic treatment, and/or administration in central nervous system structures involved in the modulation of anxiety induced by empathy for nociception in mice.