Assessment of a model to study Autism Spectrum Disorder: Investigation of the role of oxytocin in neuropathic pain-induced nociception in male and female mice.

• Grant number: 24/05415-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: December 31, 2025
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Azair Liane Matos Do Canto de Souza
• Grantee: Isabella Silva Garcia Dias
• Host Institution: Centro de Educação e Ciências Humanas (CECH). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

The success of social interaction is a necessary condition for human survival anddepends on the ability to comprehend the intentions and emotions of others. Empathy isan important interpersonal phenomenon that allows understanding and experiencingemotions that the other is feeling. Like human, empathy can be observed in other animalspecies, such as rodents. Recent studies have shown that living with male and femalemice, housed in pairs with a conspecific subject to chronic pain, increases behavioranxiogenic-like and nociceptive response in observer mice subjected to the abdominalwrithing test, showing that pain can undergo social modulation. Neuropsychiatricconditions that involve impairments in social behavior or the ability to empathize, suchas Autism Spectrum Disorder (ASD), may be associated with dysregulation inneuropeptide levels, such as oxytocin. It has been demonstrated that atosiban (anoxytocin receptor antagonist) prevents empathy responses related to increased anxietyand hypernociception in male and female mice. Considering these findings, this studyhas as aims to investigate the effects of oxytocin modulating the anxiety and painhypersensitivity induced by a male and female mouse cohabiting with a partnerssubjected to sciatic nerve constriction. In this study, male and female Swiss mice will behoused in quartets for 28 days. Then, they will be divided into two groups: sciatic nerveconstricted designated as pain demonstrators [CNC; i.e., one animal of each quartet wassubjected to sciatic nerve constriction (SNC)], and cagemate sham (S; a similarprocedure but with no nerve constriction), and returning to living with conspecificcagemate CNC or Sham demonstrator will be referred to as pain observers (Ob-CNC) ornot (Ob-Sham), for further 14 days. On the 26th, 27th, and 28th day, a divider will beintroduced into the box for 15 minutes, maintaining the conspecifics' sense of smell andvision. On the 28th day, observer mice (Ob-CNC and Ob-S) will receive subcutaneous(s.c.) injections of saline/saline, atosiban (0.5 mg/kg, s.c.)/saline, saline/oxytocin (0.5,1.0 and 5.0 mg/kg, s.c.) and atosiban (0.5 mg/kg, s.c.)/oxytocin (0.5, 1.0 and 5.0 mg/kg,s.c.). Twenty-five minutes after the last injection, each animal will be individually testedfor 5 minutes in the elevated plus-maze (EPM), to record anxiety measures. Then, micewill receive the injection of 0.1 mL.10 g-1 b. w. of 0.6% acetic acid intraperitoneally(i.p.), the nociceptive response will be assessed by recording the number of abdominalwrithes exhibited by the animals (Ob-CNC or Ob-S) for 5 min. At the end of the anxietyand nociception tests, CNC and S mice will be evaluated on the hot plate, to confirm theeffectiveness of the constriction surgery.Keywords: social contagion, oxytocin, anxiety, nociception, empathy, mice.