The neural circuitry that mediates mood under normal and abnormal conditions remains
incompletely understood. Most attention in the field has focused on hippocampal and
frontal cortical regions for their role in depression and antidepressant action. While
these regions no doubt play important roles in these phenomena, there is compelling
evidence that other brain regions are also involved. Here we focus on the potential
role of the nucleus accumbens (NAc; ventral striatum) and its dopaminergic input from
the ventral tegmental area (VTA), which form the mesolimbic dopamine system, in depression.
The mesolimbic dopamine system is most often associated with the rewarding effects
of food, sex, and drugs of abuse. Given the prominence of anhedonia, reduced motivation,
and decreased energy level in most individuals with depression, we propose that the
NAc and VTA contribute importantly to the pathophysiology and symptomatology of depression
and may even be involved in its etiology. We review recent studies showing that manipulations
of key proteins (e.g. CREB, dynorphin, BDNF, MCH, or Clock) within the VTA-NAc circuit
of rodents produce unique behavioral phenotypes, some of which are directly relevant
to depression. Studies of these and other proteins in the mesolimbic dopamine system
have established novel approaches to modeling key symptoms of depression in animals,
and could enable the development of antidepressant medications with fundamentally
new mechanisms of action.
Key Words
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Article info
Publication history
Published online: March 27, 2006
Accepted:
September 8,
2005
Received in revised form:
September 2,
2005
Received:
July 19,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
