title: The role of the medial prefrontal cortex in regulating social familiarity-induced anxiolysis.
abstract: Overcoming specific fears and subsequent anxiety can be greatly enhanced by the presence of familiar social partners, but the neural circuitry that controls this phenomenon remains unclear. To overcome this, the social interaction (SI) habituation test was developed in this lab to systematically investigate the effects of social familiarity on anxiety-like behavior in rats. Here, we show that social familiarity selectively reduced anxiety-like behaviors induced by an ethological anxiogenic stimulus. The anxiolytic effect of social familiarity could be elicited over multiple training sessions and was specific to both the presence of the anxiogenic stimulus and the familiar social partner. In addition, socially familiar conspecifics served as a safety signal, as anxiety-like responses returned in the absence of the familiar partner. The expression of the social familiarity-induced anxiolysis (SFiA) appears dependent on the prefrontal cortex (PFC), an area associated with cortical regulation of fear and anxiety behaviors. Inhibition of the PFC, with bilateral injections of the GABAA agonist muscimol, selectively blocked the expression of SFiA while having no effect on SI with a novel partner. Finally, the effect of D-cycloserine, a cognitive enhancer that clinically enhances behavioral treatments for anxiety, was investigated with SFiA. D-cycloserine, when paired with familiarity training sessions, selectively enhanced the rate at which SFiA was acquired. Collectively, these outcomes suggest that the PFC has a pivotal role in SFiA, a complex behavior involving the integration of social cues of familiarity with contextual and emotional information to regulate anxiety-like behavior.
authors.affiliation: 1] Graduate Program in Medical Neuroscience, Indiana University School of Medicine, Indianapolis, IN, USA [2] Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lungwitz
authors.affiliation: Departments of Psychiatry & Cell Biology and Physiology; UNC Neuroscience Center and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, NC, USA.
authors.forename: Garret D
authors.initials: GD
authors.lastname: Stuber
authors.affiliation: 1] Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Anatomy and Cellular Biology, Indiana University School of Medicine, Indianapolis, IN, USA [3] Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Johnson
authors.affiliation: Department of Anatomy and Cellular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Dietrich
authors.affiliation: Department of Anatomy and Cellular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schartz
authors.affiliation: Department of Anatomy and Cellular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Hanrahan
authors.affiliation: 1] Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA [3] Indiana Clinical and Translational Sciences Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
authors.affiliation: 1] Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Anatomy and Cellular Biology, Indiana University School of Medicine, Indianapolis, IN, USA [3] Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Truitt
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000209:etiology / Q000523:psychology* / Q000628:therapy*; D003463:Cues; D003523:Cycloserine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004777:Environment; D058785:GABA-A Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D006185:Habituation, Psychophysiologic; D007398:Interpersonal Relations; D008027:Light / Q000009:adverse effects; D008297:Male; D009118:Muscimol / Q000494:pharmacology / Q000627:therapeutic use; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000502:physiology*; D013997:Time Factors
chemical_list: D000963:Antimetabolites; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D003523:Cycloserine