Yohimbine potentiates active defensive responses to threatening stimuli in Swiss-Webster mice

Yohimbine HCl, an antagonist at alpha 2-noradrenaline receptors with putative panicogenic effects in human subjects, was administered to Swiss-Webster mice at doses of 0.5, 1.0, and 2.0 mg/kg. Animals were then tested in two defense test batteries. Yohimbine produced increases in flight from an approaching/contacting human and potentiated animals' reactions to dorsal contact. During a 5-min exposure to a cat (separated from the mouse by a wire-mesh screen) and the 15-min period thereafter, yohimbine produced a dose-dependent pattern of changes in defensive behaviors that included increases in locomotion, transits from one segment of the test chamber to another, fore- and hindpaw wall climbing, screen climbing and hanging, and roof pushing. Crouching (relative immobility while in a hunched-back posture) was notably decreased at all doses. During the postcat period, two different response patterns, "high-escape" and "low-escape," characterized in part by high and low frequencies of wall climbing, were observed in cat-exposed groups. In yohimbine-injected mice, the low-escape behavior pattern also included a tendency to avoid the segment of the test chamber closest to the cat compartment. Both patterns differed from the crouching and immobility generally exhibited by vehicle-injected, cat-exposed controls. It was suggested that yohimbine effected these behavioral changes by either potentiating neural mechanisms mediating flight or inhibiting mechanisms mediating freezing. This model may have some utility for the investigation of panicogenic and antipanic compounds and may contribute insights into the etiology of panic disorder.