The Mesolimbic Dopamine Reward Circuit in Depression
by
Nestler EJ, Carlezon WA Jr.
Department of Psychiatry and Center for Basic Neuroscience,
The University of Texas Southwestern Medical Center,
Dallas, Texas 75390-9070, USA.
eric.nestler@utsouthwestern.edu
Biol Psychiatry. 2006 Jun 15;59(12):1151-9


ABSTRACT

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.
Options
Dopamine
Selegiline
Roxindole
Tolcapone
Anhedonia
Amineptine
Amisulpride
Amantadine
Nomifensine
Pramipexole
21st Century
Methylphenidate
Drugs and Reward
Dopamine and sexual function
Dopamine, pleasure and salience
The ventral pallidum and pleasure
Dopamine deficiency and depression
Depression, dopamine and dextroamphetamine
Regulation of synapses in the nucleus accumbens
The nucleus accumbens: opioids versus cannabinoids
Hedonic zonal shifts in the medial shell of the nucleus accumbens


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