title: Activation of 5-HT2a receptors in the basolateral amygdala promotes defeat-induced anxiety and the acquisition of conditioned defeat in Syrian hamsters.
abstract: Conditioned defeat is a model in Syrian hamsters (Mesocricetus auratus) in which normal territorial aggression is replaced by increased submissive and defensive behavior following acute social defeat. The conditioned defeat response involves both a fear-related memory for a specific opponent as well as anxiety-like behavior indicated by avoidance of novel conspecifics. We have previously shown that systemic injection of a 5-HT2a receptor antagonist reduces the acquisition of conditioned defeat. Because neural activity in the basolateral amygdala (BLA) is critical for the acquisition of conditioned defeat and BLA 5-HT2a receptors can modulate anxiety but have a limited effect on emotional memories, we investigated whether 5-HT2a receptor modulation alters defeat-induced anxiety but not defeat-related memories. We injected the 5-HT2a receptor antagonist MDL 11,939 (0 mM, 1.7 mM or 17 mM) or the 5-HT2a receptor agonist TCB-2 (0 mM, 8 mM or 80 mM) into the BLA prior to social defeat. We found that injection of MDL 11,939 into the BLA impaired acquisition of the conditioned defeat response and blocked defeat-induced anxiety in the open field, but did not significantly impair avoidance of former opponents in the Y-maze. Furthermore, we found that injection of TCB-2 into the BLA increased the acquisition of conditioned defeat and increased anxiety-like behavior in the open field, but did not alter avoidance of former opponents. Our data suggest that 5-HT2a receptor signaling in the BLA is both necessary and sufficient for the development of conditioned defeat, likely via modulation of defeat-induced anxiety.
authors.affiliation: Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA. Electronic address: ctucke13@vols.utk.edu.
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Clinard
authors.affiliation: Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Lauren R
authors.initials: LR
authors.lastname: Bader
authors.affiliation: Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Sullivan
authors.affiliation: Department of Psychology, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000503:physiopathology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D004291:Dominance-Subordination; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008647:Mesocricetus; D008744:Methylamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology
chemical_list: C514172:(4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine; D001643:Bridged Bicyclo Compounds; D008744:Methylamines; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C066169:alpha-phenyl-1-(2-phenylethyl)-4-piperidinemethanol
keywords: 5-HT2a receptor; Anxiety; Basolateral amygdala; Conditioned defeat; Fear; Stress