Nebulized vasopressin penetrates CSF and improves social cognition without inducing aggression in a rhesus monkey model of autism

• 成果类型: Article
• 署名作者: Talbot, Catherine F.; Oztan, Ozge; Simmons, Sierra M. V.; Trainor, Callum; Ceniceros, Lesly C.; Nguyen, Duyen K. K.; Del Rosso, Laura A.; Garner, Joseph P.; Capitanio, John P.; Parker, Karen J.
• 署名单位: Florida Institute of Technology; Stanford University; University of California System; University of California Davis; Stanford University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12032
• DOI: 10.1073/pnas.2418635121
• 发表日期: 2024-12-03
• 关键词: oxytocin; CHILDREN; RECOGNITION; BEHAVIOR; face

摘要

Low cerebrospinal (CSF) arginine vasopressin (AVP) concentration is a biomarker of social impairment in low- social monkeys and children with autism, suggesting that AVP administration may improve primate social functioning. However, AVP administration also increases aggression, at least in neurotypical animals with intact AVP signaling. Here, we tested the effects of a voluntary drug administration method in low- social male rhesus monkeys with high autistic- like trait burden. Monkeys received nebulized AVP or placebo, using a within- subjects design. Study 1 (N = 8) investigated the effects of AVP administration on social cognition in two tests comparing responses to social versus nonsocial stimuli. Test 1: Placebo- administered monkeys lacked face recognition memory, whereas face recognition memory was rescued following AVP administration. In contrast, object recognition memory was intact and did not differ between administration conditions. Test 2: Placebo- administered monkeys did not respond to conspecific social communication cues, whereas following AVP administration, they reciprocated affiliative communication cues with species- typical affiliative responses. Importantly, AVP administration did not increase aggressive responses to conspecific aggressive or affiliative overtures. Study 2 (N = 4) evaluated the pharmacokinetics of this administration method. Following AVP nebulization, we observed a linear increase in cisternal CSF AVP levels, and a quadratic rise and fall in blood AVP levels. These findings indicate that nebulized AVP likely penetrates the central nervous system, selectively promotes species- typical responses to social information, and does not induce aggression in low- social individuals. Nebulized AVP therefore may hold promise for managing similar social symptoms in people with autism, particularly in very young or lower functioning individuals.