Brain reward circuits can be disrupted by early-life stress: Research

• Depression, drug abuse, and taking too many risks are all thought to be brought on by the dysfunction of this circuit.
• By explaining how early stress and adversity cause the reward circuit in the brain.
• They discovered that male mice’s reward behaviors are suppressed by activating this novel pathway.

By explaining how early stress and adversity cause the reward circuit in the brain to function improperly, a novel brain link may provide a new therapeutic target for the treatment of mental illness. Depression, drug abuse, and taking too many risks are all thought to be brought on by the dysfunction of this circuit.

Dr. Matt Birnie, lead author and a postdoctoral researcher, and Dr. Tallie Z. Baram, senior author and UCI Donald Bren Professor and Distinguished Professor in the Departments of Neurology and Physiology & Biophysics, Pediatrics, and Anatomy & Neurobiology, respectively, describe the cellular changes in the brain’s circuitry caused by childhood adversity.

Baram stated, “We know that early-life stress impacts the brain, but we didn’t know how until now.” Our team’s focus was on locating brain pathways that might be affected by stress. Within the reward circuit, we discovered a brand-new pathway that expresses a molecule known as corticotropin-releasing hormone, which regulates our stress responses. This brain pathway becomes overactive in response to negative experiences, as we discovered.”

She stated, “These changes to the pathway disrupt reward behaviors in mice, reducing pleasure and motivation for fun, food, and sex cues.” Such behavioral shifts, known as “anhedonia,” are linked to emotional disorders in humans. Importantly, we discovered that modern technology can restore normal reward behaviors when this pathway is silenced.

All of the CRH-expressing connections were mapped to the brain’s nucleus accumbens, which is a center for pleasure and motivation, and they discovered a new projection from the basolateral amygdala that was previously unknown. Gamma-aminobutyric acid was co-expressed by projection fibers and CRH. They discovered that male mice’s reward behaviors are suppressed by activating this novel pathway.

Male and female mice were divided into two groups for the research. One was reared in typical cages, while the other was exposed to hardship early on by spending a week in cages with limited bedding and nesting materials. When compared to mice that are typically reared, the adult males of the early adversity-experiencing mice showed little interest in sweet foods or sex cues. Contrarily, females who had experienced adversity craved sweet, rich food. Males’ normal reward behaviors were restored by inhibiting the pathway, but females’ reward behaviors remained unaffected.

“We believe that our findings provide novel insights into the influence of early-life adversity on brain development, particularly on the control of reward behaviors that are the foundation of numerous emotional disorders. Our discovery of the previously unknown function of the basolateral amygdala-nucleus accumbens brain pathway’s circuit deepens our comprehension of this intricate mechanism and identifies a significant new therapeutic target.” “Baram stated. To better comprehend the distinct and sex-specific effects of early-life adversity on behavior, additional research is required.

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