Biphasic effects of selective serotonin reuptake inhibitors on anxiety: rapid reversal of escitalopram's anxiogenic effects in the novelty-induced hypophagia test in mice?

In humans, chronic treatment with selective serotonin reuptake inhibitors (SSRIs) decreases anxiety, unlike acute treatment, which can increase anxiety. Although this biphasic pattern is observed clinically, preclinical demonstrations are rare. In an animal model of antidepressant-induced anxiolytic effects, the novelty-induced hypophagia (NIH) test, a single administration of the SSRI citalopram reportedly elicited anxiogenic-like effects, whereas three administrations over 24 h were sufficient to produce anxiolytic-like effects. Extending these findings, the present study examined the effects of acute and repeated escitalopram in a similar NIH test in a commonly used mouse strain (i.e. C57BL/6J), analyzing results with a method (i.e. survival analysis) that can model the skewed distribution of latencies to consume food and that can deal with censored data (i.e. when consumption does not occur during the test). Saline-treated mice showed robust NIH. Acute escitalopram enhanced NIH, but did so only at a dose (i.e. 32 mg/kg) that similarly enhanced hypophagia in a familiar environment. The effects of escitalopram on NIH did not significantly change after repeated (three times) administration over 24 h. Additional studies are necessary to delineate the conditions under which rapid reversal of SSRI-induced anxiety can be modeled in animals using the NIH test.