Neurochemical and Electrophysiological Events Underlying Stress-Induced Depression in an Animal Model

Abstract

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…