title: Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats.
abstract: The kappa opioid receptor (KOR) system contributes to the prodepressive and aversive consequences of stress and is implicated in the facilitation of conditioned fear and anxiety in rodents. Here, we sought to identify neural circuits that mediate KOR system effects on fear and anxiety in rats.
  
  
  
  We assessed whether fear conditioning induces plasticity in KOR or dynorphin (the endogenous KOR ligand) messenger RNA (mRNA) expression in the basolateral (BLA) and central (CeA) nuclei of the amygdala, hippocampus, or striatum. We then assessed whether microinfusions of the KOR antagonist JDTic (0-10 μg/side) into the BLA or CeA affect the expression of conditioned fear or anxiety. Finally, we examined whether fear extinction induces plasticity in KOR mRNA expression that relates to the quality of fear extinction.
  
  
  
  Fear conditioning upregulated KOR mRNA in the BLA by 65% and downregulated it in the striatum by 22%, without affecting KOR levels in the CeA or hippocampus, or dynorphin levels in any region. KOR antagonism in either the BLA or CeA decreased conditioned fear in the fear-potentiated startle paradigm, whereas KOR antagonism in the BLA, but not the CeA, produced anxiolytic-like effects in the elevated plus maze. Effective fear extinction was associated with a 67% reduction in KOR mRNA in the BLA.
  
  
  
  These findings suggest that fear conditioning and extinction dynamically regulate KOR expression in the BLA and provide evidence that the BLA and CeA are important neural substrates mediating the anxiolytic-like effects of KOR antagonists in models of fear and anxiety.
authors.affiliation: Department of Psychiatry, Behavioral Genetics Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA.
authors.forename: Allison T
authors.initials: AT
authors.lastname: Knoll
authors.forename: John W
authors.initials: JW
authors.lastname: Muschamp
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Daws
authors.forename: Deveroux
authors.initials: D
authors.lastname: Ferguson
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.forename: Edward G
authors.initials: EG
authors.lastname: Meloni
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
authors.forename: Christine
authors.initials: C
authors.lastname: Konradi
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004399:Dynorphins / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C433814:7-hydroxy-N-(1-((4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl)methyl)-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide; D010880:Piperidines; D017473:Receptors, Opioid, kappa; D044005:Tetrahydroisoquinolines; D004399:Dynorphins