The selective serotonin reuptake inhibitor citalopram increases fear after acute treatment but reduces fear with chronic treatment: a comparison with tianeptine.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) are efficacious in the treatment of a variety of fear or anxiety disorders. Although they inhibit the reuptake of serotonin within hours of administration, therapeutic improvement only occurs after several weeks. In this study, we used fear conditioning to begin to understand how acute and chronic SSRI treatment might differentially affect well-characterized fear circuits.


METHODS
We evaluated the effects of acute and chronic treatment with the SSRI citalopram on the acquisition of auditory fear conditioning. To further understand the role of serotonin in modulating fear circuits, we compared these effects with those of acute and chronic administration of the antidepressant tianeptine, a purported serotonin reuptake enhancer.


RESULTS
We found that acute administration of the SSRI citalopram enhanced acquisition, whereas chronic treatment reduced the acquisition of auditory fear conditioning. In comparison, treatment with tianeptine had no effect acutely but also reduced the acquisition of tone conditioning when administered chronically.


CONCLUSIONS
Our findings with citalopram are consistent with the clinical effects of SSRI treatment seen in patients with anxiety disorders, in which anxiety is often increased during early stages of treatment and decreased after several weeks of treatment. The findings also indicate that auditory fear conditioning can be a useful tool in understanding differences in the effects of short-term and long-term antidepressant treatment with serotonergic medications.
Burghardt
Nesha S
NS
W.M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003, USA.
Sullivan
Gregory M
GM
McEwen
Bruce S
BS
Gorman
Jack M
JM
LeDoux
Joseph E
JE
D000161:Acoustic Stimulation; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D015283:Citalopram / Q000494:pharmacology*; D003213:Conditioning, Psychological; D005239:Fear / Q000187:drug effects*; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013841:Thiazepines / Q000494:pharmacology*; D013997:Time Factors
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D013841:Thiazepines; D015283:Citalopram; C050504:tianeptine