Background
Selective serotonin reuptake inhibitors (SSRIs) effectively treat various anxiety
disorders, although symptoms of anxiety are often exacerbated during early stages
of treatment. We previously reported that acute treatment with the SSRI citalopram
enhances the acquisition of auditory fear conditioning, which is consistent with the
initial anxiogenic effects reported clinically. Here, we extend our findings by assessing
the effects of acute SSRI treatment on the expression of previously acquired conditioned
fear.
Methods
Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested
after drug treatment the following day. This protocol more closely resembles the clinical
setting than pre-conditioning treatment, because it evaluates effects of treatment
on a pre-existing fear rather than on the formation of a new fear memory.
Results
A single pre-testing injection of the SSRIs citalopram or fluoxetine significantly
increased fear expression. There was no effect of the antidepressant tianeptine or
the norepinephrine reuptake inhibitor tomoxetine, indicating that this effect is specific
to SSRIs. The SSRI-induced enhancement in fear expression was not blocked by tropisetron,
a 5-HT3 receptor antagonist, but was blocked by SB 242084, a specific 5-HT2C receptor antagonist.
Conclusions
Enhanced activation of 5-HT2C receptors might be a mechanism for the anxiogenic effects of SSRIs observed initially
during treatment.
Key Words
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Article info
Publication history
Published online: May 26, 2007
Accepted:
November 22,
2006
Received in revised form:
October 27,
2006
Received:
May 21,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
