Evaluation of a model to study Autism Spectrum Disorder: investigating the role of the interaction between endocannabinoid and oxytocinergic neurotransmissions in anxiety and nociception induced by the neuropathic pain model in male and female mice

• Grant number: 24/15356-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: December 31, 2025
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Azair Liane Matos Do Canto de Souza
• Grantee: João Pedro Janson de Oliveira
• Host Institution: Centro de Educação e Ciências Humanas (CECH). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Pain is a complex response with social implications that can influence the behavior of individuals socializing with an individual in distress. Understanding and experiencing the emotions of others is known as empathy, a phenomenon observed in humans and other species, including rodents. Studies have shown that mice cohabiting with conspecifics experiencing chronic pain, in pairs or quartets, exhibit anxious behaviors and increased pain sensitivity (hypernociception), showing that pain can undergo social modulation. The oxytocinergic and endocannabinoid systems modulate social interactions, pain responses, anxiety, and empathy. In this context, the empathy response related to increased anxiety and hypernociception in male and female mice was not reversed by atosiban, an antagonist of oxytocin receptors. Autism Spectrum Disorder (ASD) is a neurobiological developmental disorder that affects social communication and behavior. People with ASD have difficulty demonstrating empathy and the ability to understand and share others' feelings. Recent studies have shown that systemic cannabidiol (CBD) administration reversed empathy-related responses associated with increased anxiety and nociception in male mice. Based on the evidence presented, we aim to investigate the role of the interaction between endocannabinoid neurotransmission and oxytocinergic neurotransmission in modulating anxiety and nociception induced by the neuropathic pain model in male and female mice. Based on the evidence presented, we aim to investigate the role of the interaction between endocannabinoid neurotransmission and oxytocinergic neurotransmission in modulating anxiety and nociception induced by the neuropathic pain model in male and female mice. In this study, male and female Swiss albino mice will be housed in quartets during a 28-day cohabitation protocol. On the 14th day of cohabitation, one animal from each quartet will undergo sciatic nerve constriction surgery (CNC) or sham (S), a similar procedure but with no nerve constriction, returning to cohabitate with conspecifics for an additional 14 days. On the 26th, 27th, and 28th days, a divider will be introduced into the vivarium box for 15 minutes, maintaining olfactory and visual contact with conspecifics. On the 28th day, mice observer (Ob) that cohabited with their CNC (Ob-CNC) or S (Ob-S) conspecifics will receive injections of saline, atosiban [0.5 mg/kg, subcutaneous (s.c.)], Experiment 1; saline, cannabidiol (10 and 30 mg/kg, s.c.), Experiment 2; and saline/saline, atosiban (0.5 mg/kg, s.c.)/saline, saline/cannabidiol (10 and 30 mg/kg, s.c.), or atosiban (0.5 mg/kg, s.c.)/cannabidiol (10 and 30 mg/kg, s.c.), Experiment 3. After 25 minutes of the second injection, each animal will be individually tested for 5 minutes in the elevated plus maze (EPM) to record anxiety indices. Subsequently, Ob-CNC and Ob-S mice will receive a 0.6% acetic acid injection [10 ml/kg, intraperitoneal (i.p.)] for a 5-minute evaluation of abdominal writhing in the presence of the conspecific (CNC or S). CNC and S mice not undergoing the abdominal writhing test will be subjected to the hot plate test to confirm the effectiveness of the constriction surgery.