Acute Selective Serotonin Reuptake Inhibitors Increase Conditioned Fear Expression: Blockade With a 5-HT2C Receptor Antagonist

• Published in: Biological psychiatry (1969) Vol. 62; no. 10; pp. 1111 - 1118
• Main Authors: Burghardt, Nesha S, Bush, David E.A, McEwen, Bruce S, LeDoux, Joseph E
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 15.11.2007
• Subjects: Biological and medical sciences; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; serotonin; fear conditioning; Amygdala; citalopram; 5-HT 2C receptor; 5-HT 3 receptor; Affect affectivity; Psychotropic; Central nervous system; Reuptake inhibitor; Encephalon; Citalopram; Selective serotonin reuptake inhibitor; Antidepressant agent; Antagonist; Conditioning; 5-HT2c receptor; Amygdaloid nucleus; 5-HT2C serotonin receptor; 5-HT3 receptor; Serotonin; Acute; Basal ganglion; Emotion emotionality; Fear; Chemotherapy; Treatment; 5-HT3 Serotonine receptor; Neurotransmitter
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2006.11.023

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.