Serotonin reuptake inhibitors reduce conditioned fear stress-induced freezing behavior in rats

Conditioned fear stress (CFS)-induced freezing behavior has been proposed as an animal model of anxiety. In the present study, freezing was used to determine the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs), which are reported to be clinically effective in anxiety disorders. The duration of freezing behavior was reduced by acute treatment with the SSRIs citalopram (1-10 mg/kg) and fluvoxamine (3-30 mg/kg). Acute treatment with the serotonin (5-HT)/noradrenaline (NA) mixed reuptake inhibitor milnacipran (3-30 mg/kg) also attenuated CFS-induced freezing, while acute treatment with the NA reuptake inhibitors maprotiline and ORG4428, and the dopamine (DA) reuptake inhibitor GBR12909 failed to alter CFS-induced freezing. These results indicate that facilitation of 5-HT availability in the brain produced by 5-HT reuptake inhibition reduces CFS-induced freezing behavior. CFS may be a useful model for detecting the anxiolytic potential of 5-HT reuptake inhibitors.