Efficacy of Chronic Antidepressant Treatments in a New Model of Extreme Anxiety in Rats

Abstract

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders.