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Keywords:

  • norepinephrine;
  • dopamine;
  • galanin;
  • animal model;
  • locus coeruleus;
  • ventral tegmentum;
  • rat;
  • motor activity;
  • anhedonia

Abstract

A hypothesis is presented that attempts to describe the mechanism by which noradrenergic neurons in the brain influence dopaminergic neurons to produce behavioral changes seen in depression. The historical background pointing to a norepinephrine (NE)-dopamine (DA) interaction in depression is described. This interaction is suggested by numerous observations indicating that whereas NE is important in therapy and pathogenesis of depression, basic research implicates DA in depression-related behavioral responses (motor activity changes, hedonic response) much more so than NE. The hypothesized NE-DA interaction is introduced in relation to an animal model (stress-induced behavioral depression) that has traced depressive symptomatology to abnormal activity (hyperresponsivity) of locus coeruleus (LC) neurons. Based on recent data by Grenhoff et al. (1993; J Neural Transm 93:11–25), it is suggested that the augmented burst firing of LC neurons found in behavioral depression releases galanin from LC axon terminals, and this inhibits (hyper-polarizes) DA neurons in the ventral tegmentum (VTA) to mediate depression-related behavioral changes. Initial results showing that microinfusion of galanin into the VTA decreases spontaneous and swim-test motor activity of animals are described. Depression 3:225–245 (1995/1996). © 1996 Wiley-Liss, Inc.