title: Effects of oxytocin on serotonin 1B agonist-induced autism-like behavior in mice.
abstract: Social impairments in autism remain poorly understood and without approved pharmacotherapies. Novel animals models are needed to elucidate mechanisms and evaluate novel treatments for the social deficits in autism. Recently, serotonin 1B receptor (5-HT1B) agonist challenge in mice was shown to induce autism-like behaviors including perseveration, reduced prepulse inhibition, and delayed alternation deficits. However, the effects of 5-HT1B agonists on autism-related social behaviors in mice remain unknown. Here, we examine the effects of 5-HT1B agonist challenge on sociability and preference for social novelty in mice. We also examine the effects of 5-HT1B agonist treatment on average rearing duration, a putative rodent measure of non-selective attention. Non-selective attention is an associated feature of autism that is also not well understood. We show that 5-HT1B receptor activation reduces sociability, preference for social novelty, and rearing in mice. In addition, we examine the ability of oxytocin, an off-label treatment for the social impairments in autism, to reverse 5-HT1B agonist-induced social and attention deficits in mice. We show that oxytocin restores social novelty preference in mice treated with a 5-HT1B agonist. We also show that oxytocin attenuates 5-HT1B agonist-induced sociability and rearing deficits in mice. Our results suggest that 5-HT1B agonist challenge provides a useful pharmacological mouse model for aspects of autism, and implicate 5-HT1B in autism social and attention deficits. Moreover, our findings suggest that oxytocin may treat the social deficits in autism through a mechanism involving 5-HT1B.
authors.affiliation: Department of Psychology, Wittenberg University, Springfield, OH 45501 United States.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Lawson
authors.affiliation: Department of Psychology, Wittenberg University, Springfield, OH 45501 United States.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Gray
authors.affiliation: Department of Psychology, Wittenberg University, Springfield, OH 45501 United States; Neuroscience Program, Wittenberg University, Springfield, OH 45501, United States. Electronic address: woehrlen@wittenberg.edu.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Woehrle
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000139:chemically induced / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D010121:Oxytocin / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D012919:Social Behavior
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D058825:Serotonin 5-HT1 Receptor Agonists; D012701:Serotonin; D010121:Oxytocin
keywords: Autism spectrum disorder; Mouse model; Non-selective attention; Oxytocin; Serotonin 1B receptor; Three-chambered social test