Pharmacological depletion of serotonin in the basolateral amygdala complex reduces anxiety and disrupts fear conditioning

Philip Johnson, Andrei Molosh, Stephanie D. Fitz, Dave Arendt, Gerald A. Deehan, Lauren M. Federici, Cristian Bernabe, Eric Engleman, Zachary Rodd, Christopher A. Lowry, Anantha Shekhar

Research output: Contribution to journalArticle

23 Scopus citations

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 5 days, 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.

Original languageEnglish (US)
Pages (from-to)174-179
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume138
DOIs
StatePublished - Nov 1 2015

    Fingerprint

Keywords

  • 5,7-dht
  • 5-ht
  • Amygdala
  • Anxiety
  • Dorsal raphe
  • Fear
  • Sert

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology
  • Toxicology
  • Behavioral Neuroscience
  • Biological Psychiatry

Cite this