This paper has described an animal (rodent) model of depression in which depression-like characteristics are produced by exposure of animals to stressful events that they cannot control. This model, called "stress-induced depression," appears to be mediated by stress-induced changes in brain norepinephrine (NE), and evidence now indicates that a large depletion of NE in the Locus Coeruleus region of the brain stem (LC) is critical for producing the behavioral disturbance seen in this model. To explain the functional significance of NE depletion in the LC, it has been suggested that this change results in decreased stimulation, (i.e., functional blockade) of alpha-2 receptors that normally inhibit firing of LC neurons. Consequently, LC neurons should be disinhibited in stress-induced depression. The final part of this paper describes findings from electrophysiological measurement of LC activity. Prior to measuring changes occurring in stress-induced depression, studies examined the basic role played by alpha-2 receptors in LC activity. These receptors were found to regulate the responsivity of LC neurons to excitatory stimuli, so that pharmacological blockade of these receptors increased the firing of LC neurons to excitatory input. When LC activity was then measured in stressed animals showing behavioral depression, responsivity of LC neurons to excitatory input was elevated in comparison to animals not exposed to stress. Also, administration of an alpha-2 blocking drug could not increase responsivity of LC neurons in stressed animals, which further indicated that alpha-2 receptors in the LC region were functionally blocked in these animals. Finally, the amount that LC neurons increased their firing to an excitatory stimulus (i.e., an index of alpha-2 receptor blockade) was highly correlated with the amount of behavioral depression seen in an activity test conducted just prior to electrophysiological measurement. These electrophysiological findings indicate that LC neurons are disinhibited in stress-induced depression, and that this disinhibition is particularly characterized by increased responsivity of LC neurons to excitatory input, which is indicative of alpha-2 receptor blockade. These findings further support the view that the LC is involved in stress-induced depression, and are consistent with a proposed mechanism that attributes behavioral disturbance in the model to disinhibition of LC neurons arising from subnormal activation of inhibitory alpha-2 receptors.