Selective serotonin reuptake inhibitor reduces conditioned fear through its effect in the amygdala.

Selective serotonin reuptake inhibitors are first-line treatment for most anxiety disorders, but their mechanism of anxiolytic action has not been clarified. Selective serotonin reuptake inhibitors are anxiolytic in conditioned fear stress (re-exposure to an environment paired previously with inescapable electric footshocks). To clarify the brain regions where selective serotonin reuptake inhibitors act, we examined the effect of microinjection of the selective serotonin reuptake inhibitor, citalopram, into the amygdala, medial prefrontal cortex and mediodorsal nucleus of the thalamus on freezing behavior, an index of fear, induced by conditioned fear stress. Bilateral injection of citalopram into the amygdala before testing reduced freezing significantly, while bilateral injection into the medial prefrontal cortex or mediodorsal nucleus of the thalamus did not. These results suggest that the anxiolytic effect of a selective serotonin reuptake inhibitor in conditioned fear is mediated by its effect in the amygdala, and support the hypothesis of serotonin function in anxiety by which facilitation of serotonin neurotransmission decreases anxiety.
AuthorsTakeshi Inoue, Xiao Bai Li, Tomohiro Abekawa, Yuji Kitaichi, Takeshi Izumi, Shin Nakagawa, Tsukasa Koyama
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 497 Issue 3 Pg. 311-6 (Aug 30 2004) ISSN: 0014-2999 [Print] Netherlands
PMID15336949 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Serotonin Uptake Inhibitors
  • Citalopram
  • Amygdala (drug effects, physiology)
  • Animals
  • Behavior, Animal (drug effects)
  • Citalopram (administration & dosage, pharmacology)
  • Conditioning, Operant (drug effects)
  • Fear (drug effects, psychology)
  • Male
  • Mediodorsal Thalamic Nucleus (physiology)
  • Microinjections
  • Motor Activity (drug effects)
  • Prefrontal Cortex (physiology)
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Uptake Inhibitors (administration & dosage, pharmacology)

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