A series of three experiments were carried out to test the hypothesis (“motor activation deficit” hypothesis) that the avoidance-escape deficits observed following certain highly stressful conditions result from changes in activity of noradrenergic (or other monominergic) neural systems. These studies indicate that: (1) Depletion of monamines by a single injection of tetrabenazine produces an active avoidance-escape deficit when the avoidance-escape response involves a relatively high degree of motor activity but not when a minimum of motor activity is required. This parallels results found when animals are acutely exposed to a stressor prior to avoidance-escape testing. (2) Daily injections of tetrabenazine for a period of two weeks, like daily exposure to inescapable shock for the same period of time, markedly attenuates the magnitude of the avoidance-escape deficit produced by either a single injection of tetrabenazine or single session of inescapable shock. (3) Decreasing the stress-induced depletion of monamines by the use of an MAO inhibitor serves to protect the animals from the effects of inescapable shock, markedly reducing the avoidance-escape deficit produced by such shock. It is concluded that these results are consistent with the motor activation deficit hypothesis.