Chronic Stress Can Result in Loss of Pleasure and Depression

Scientists at the Medical College of Georgia looked in the hypothalamus, key to functions like releasing hormones and regulating hunger, thirst, mood, sex drive and sleep, at a population of neurons called the proopiomelanocortin, or POMC, neurons, in response to 10 days of chronic, unpredictable stress. 

They found the stressors increased spontaneous firing of these POMC neurons in male and female mice, says corresponding author Xin-Yun Lu, MD, PhD.

When they directly activated the neurons, rather than letting stress increase their firing, it also resulted in the apparent inability to feel pleasure, called anhedonia.

The results indicate POMC neurons are “both necessary and sufficient” to increase susceptibility to stress, and their increased firing is a driver of resulting behavioral changes like depression. In fact, stress overtly decreased inhibitory inputs onto POMC neurons, Lu says.

The POMC neurons are in the arcuate nucleus, or ARC, of the hypothalamus, a bow-shaped brain region already thought to be important to how chronic stress affects behavior.

Occupying the same region is another population of neurons, called AgRP neurons, which are important for resilience to chronic stress and depression.

In the face of chronic stress, Lu’s lab reported that AgRP activation goes down as behavioral changes like anhedonia occur, and that when they stimulated those neurons the behaviors diminished. Her team also wanted to know what chronic stress does to the POMC neurons.

AgRP neurons, better known for their role in us seeking food when we are hungry, are known to have a yin-yang relationship with POMC neurons: When AgRP activation goes up, for example, POMC activation goes down.

“If you stimulate AgRP neurons it can trigger immediate, robust feeding,” Lu says. 

Their studies found that chronic stress disrupts the yin-yang balance between these two neuronal populations leading to behavioral changes. 

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Sources:

Xing Fang, Yuting Chen, Jiangong Wang, Ziliang Zhang, Yu Bai, Kirstyn Denney, Lin Gan, Ming Guo, Neal L. Weintraub, Yun Lei, Xin-Yun Lu. Increased intrinsic and synaptic excitability of hypothalamic POMC neurons underlies chronic stress-induced behavioral deficits. Molecular Psychiatry, 2022; DOI: 10.1038/s41380-022-01872-5

Medical College of Georgia at Augusta University. “When chronic stress activates these neurons, behavioral problems like loss of pleasure, depression result.” ScienceDaily. ScienceDaily, 24 January 2023. <www.sciencedaily.com/releases/2023/01/230124101601.htm>.

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