title: Chronic antidepressant treatment impairs the acquisition of fear extinction.
abstract: BACKGROUND
  Like fear conditioning, the acquisition phase of extinction involves new learning that is mediated by the amygdala. During extinction training, the conditioned stimulus is repeatedly presented in the absence of the unconditioned stimulus, and the expression of previously learned fear gradually becomes suppressed. Our previous study revealed that chronic treatment with a selective serotonin reuptake inhibitor (SSRI) impairs the acquisition of auditory fear conditioning. To gain further insight into how SSRIs affect fear learning, we tested the effects of chronic SSRI treatment on the acquisition of extinction.
  
  
  METHODS
  Rats were treated chronically (22 days) or subchronically (9 days) with the SSRI citalopram (10 mg/kg/day) before extinction training. The results were compared with those after chronic and subchronic treatment with tianeptine (10 mg/kg/day), an antidepressant with a different method of action. The expression of the NR2B subunit of the N-methyl-D-aspartate receptor in the amygdala was examined after behavioral testing.
  
  
  RESULTS
  Chronic but not subchronic administration of citalopram impaired the acquisition of extinction and downregulated the NR2B subunit of the N-methyl-D-aspartate receptor in the lateral and basal nuclei of the amygdala. Similar behavioral and molecular changes were found with tianeptine treatment.
  
  
  CONCLUSIONS
  These results provide further evidence that chronic antidepressant treatment can impair amygdala-dependent learning. Our findings are consistent with a role for glutamatergic neurotransmission in the final common pathway of antidepressant treatment.
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032-2695, USA. nsb2113@columbia.edu
authors.forename: Nesha S
authors.initials: NS
authors.lastname: Burghardt
authors.forename: Torfi
authors.initials: T
authors.lastname: Sigurdsson
authors.forename: Jack M
authors.initials: JM
authors.lastname: Gorman
authors.forename: Bruce S
authors.initials: BS
authors.lastname: McEwen
authors.forename: Joseph E
authors.initials: JE
authors.lastname: LeDoux
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects*; D015283:Citalopram / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects*; D004334:Drug Administration Schedule; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007859:Learning Disabilities / Q000139:chemically induced*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D013841:Thiazepines; D015283:Citalopram; C050504:tianeptine