Intravenous cocaine precipitates panic-like flight responses and lasting hyperdefensiveness in laboratory rats

There is an emerging body of clinical evidence that cocaine use in humans can result in serious fear or panic-related emotional disturbances. The present study evaluated the effects of intravenous cocaine administration upon defensive responses of rats to a threatening conspecific in a test situation, an oval runaway, permitting the display of the full range of the rat defensive repertoire. A battery of tests was employed to evaluate avoidance/escape, flight, freezing, defensive upright and defensive attack behaviors. In the first experiment male Long-Evans rats implanted with a chronic indwelling jugular catheter were placed in the runway and tested immediately after administration of either 0, 1, or 4 mg/kg of cocaine hydrochloride. The 4-mg/kg dose produced a dramatic flight response, the direction of which depended upon the direction of the approaching threat source. The same dose produced increased defensive upright postures during forced contact with the stimulus animal. Experiment 2 examined the time course for cocaine-induced hyperdefensiveness. Rats were administered either saline or 4 mg/kg cocaine intravenously and were tested following a delay of either 0, 5, 15, or 30 min following infusion. Cocaine-treated rats again displayed high levels of flight, which declined with increased time between infusion and testing. However, increased defensiveness persisted even at the 30 min delay for several defensive measures including avoidance, freezing, and defensive upright posture. Thus, following an initial period of rapid flight with intravenous cocaine administration, there was a lasting hyperdefensiveness in cocaine-treated rats. The present results suggest that cocaine may exert its panic-producing effects by acting upon neurobehavioral systems subserving defensive behavior, and that understanding of these systems is critical for understanding the neurobiology of panic disorder.