title: Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning.
abstract: The basolateral and lateral amygdala nuclei complex (BLC) is implicated in a number of emotional responses including conditioned fear and social anxiety. Based on previous studies demonstrating that enhanced serotonin release in the BLC leads to increased anxiety and fear responses, we hypothesized that pharmacologically depleting serotonin in the BLC using 5,7-dihydroxytryptamine (5,7-DHT) injections would lead to diminished anxiety and disrupted fear conditioning. To test this hypothesis, 5,7-DHT(a serotonin-depleting agent) was bilaterally injected into the BLC. Desipramine (a norepinephrine reuptake inhibitor) was systemically administered to prevent non-selective effects on norepinephrine. After 5days, 5-7-DHT-treated rats showed increases in the duration of social interaction (SI) time, suggestive of reduced anxiety-like behavior. We then used a cue-induced fear conditioning protocol with shock as the unconditioned stimulus and tone as the conditioned stimulus for rats pretreated with bilateral 5,7-DHT, or vehicle, injections into the BLC. Compared to vehicle-treated rats, 5,7-DHT rats had reduced acquisition of fear during conditioning (measured by freezing time during tone), also had reduced fear retrieval/recall on subsequent testing days. Ex vivo analyses revealed that 5,7-DHT reduced local 5-HT concentrations in the BLC by ~40% without altering local norepinephrine or dopamine concentrations. These data provide additional support for 5-HT playing a critical role in modulating anxiety-like behavior and fear-associated memories through its actions within the BLC.
authors.affiliation: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA,. Electronic address: philjohn@iupui.edu.
authors.forename: Philip L
authors.initials: PL
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Molosh
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Fitz
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Dave
authors.initials: D
authors.lastname: Arendt
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Deehan
authors.affiliation: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Federici
authors.affiliation: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Bernabe
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engleman
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.affiliation: Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Lowry
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Anantha
authors.initials: A
authors.lastname: Shekhar
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D003463:Cues; D003891:Desipramine / Q000494:pharmacology; D004597:Electroshock; D005239:Fear / Q000187:drug effects* / Q000523:psychology*; D007398:Interpersonal Relations; D008297:Male; D008845:Microinjections; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D003891:Desipramine
keywords: 5,7-dht; 5-ht; Amygdala; Anxiety; Dorsal raphe; Fear; Sert