The Mesolimbic Dopamine Reward Circuit in Depression
Nestler EJ, Carlezon WA Jr.
Department of Psychiatry and Center for Basic Neuroscience (EJN),
The University of Texas Southwestern Medical Center,
Biol Psychiatry. 2006 Mar 25;
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.
Dopamine and thought
Dopamine and the genes
Dopamine and reward-signalling
Dopamine deficiency and depression
Dopamine: learning likes and dislikes
Depression, dopamine and dextroamphetamine
Mesolimbic medium spiny neurons and pleasure
Regulation of synapses in the nucleus accumbens
The nucleus accumbens: opioids versus cannabinoids
Hedonic zonal shifts in the medial shell of the nucleus accumbens