Effects of acute citalopram on the expression of conditioned freezing in naive versus chronic citalopram-treated rats

An acute challenge with selective serotonin (5-HT) reuptake inhibitors (SSRIs) reduces the conditioned freezing in rats, a model of anxiety. The increase in the 5-HT levels in the nerve terminal induced by SSRIs is closely related to its pharmacological effects. Clinically, SSRIs exert an anxiolytic effect after chronic treatment. The effects of repeated treatment with citalopram on conditioned freezing in rats were examined in the present study. Acute citalopram (10 mg/kg) reduced freezing at a short post-training interval (1 day) significantly. While the effect of citalopram (10 mg/kg) on freezing was diminished by prolonging the interval between conditioning and the exposure to conditioned fear stress, repeated citalopram (10 mg/kg) injection twice daily for 7 days restored the inhibitory effect of acute challenge of citalopram (10 mg/kg) on freezing. By prolonging the period between conditioning and exposure to conditioned fear stress, this model may have a more precise predictive validity of anxiety disorder as an animal model.