*N. S. BURGHARDT1, D. E. A. BUSH1, B. S. MCEWEN2, J. E. LEDOUX1;
1Ctr for Neural Sci, New York Univ, New York, NY, 2Lab of Neuroendocrinology, Rockefeller Univ, New York, NY.

SSRIs are effective in treating a range of 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 anxiogenic effects found clinically. Here, we extend our findings by testing the effects of acute SSRI treatment on the expression of previously acquired conditioned fear. Rats underwent fear conditioning drug-free. Tone-evoked fear responses were tested after drug treatment the following day. This paradigm more closely resembles the clinical setting than pre-conditioning treatment, since it evaluates the effects of treatment on a pre-existing fear, rather than on the formation of a new fear memory. We found that 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 systemically administered tropisetron, a 5-HT3 receptor antagonist, but was blocked by systemically administered SB 242084, a specific 5-HT2C receptor antagonist. Therefore, enhanced activation of 5-HT2C receptors may be a mechanism for the anxiogenic effects of SSRIs observed initially during treatment. Given the important role of the amygdala in auditory fear conditioning, it is possible that the 5-HT2C receptors located in this brain region may be involved. Our findings suggest that co-administration of 5-HT2C receptor antagonists with SSRIs may help prevent the increase in anxiety often reported during early stages of treatment..
Support Contributed By: P50 MH058911;R01 MH046516 ;K05 MH067048

Program No. 370.8/KK26
Poster presentation:Monday, Oct 16, 2006, 9:00 AM -10:00 AM
Location: Georgia World Congress Center: Halls B3-B5