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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.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Burghardt NS,Sigurdsson T,Gorman JM,McEwen BS,LeDoux JE

doi

10.1016/j.biopsych.2012.10.012

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

1078-86

issue

11

eissn

0006-3223

issn

1873-2402

pii

S0006-3223(12)00925-0

journal_volume

73

pub_type

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