Altered activity of the locus coeruleus in an animal model of depression.

In rats showing depression of active behavior, locus coeruleus (LC) neurons were not inhibited as they are normally; in particular, electrophysiologic recording showed LC neurons were hyperresponsive to excitatory input. Moreover, the degree to which LC neurons of individual animals were hyperresponsive correlated positively with the degree to which active behavior was depressed. Recently, hyperresponsiveness of LC neurons has been found to occur when the inhibitory influence of alpha 2-receptors on LC firing is blocked. Pharmacologic blockade of alpha 2-receptors in animals showing behavioral depression was not able to increase responsiveness of LC neurons as in normal animals, indicating that alpha 2-receptors were subnormally activated in behavioral depression. These results show that activity of the principle noradrenergic cell group in the brain, the locus coeruleus, is altered in behavioral depression in an animal model, and suggest that abnormalities in this system and its regulatory elements, such as alpha 2-receptors, may be present in some types of clinical depression.