Effects of Social Isolation on Ventral Tegmental Area Opioid Receptor Expression
Maya Patel1, Daniel Chandler1
1Rowan Virtua School of Osteopathic Medicine
Objective:
Understanding the molecular and physiological mechanisms underlying social isolation (SI) may lead to improved therapeutic interventions for substance use disorders and mental illnesses.
Background:

Loneliness is a growing epidemic and an uptick was noted after the onset of the CVOID-19 pandemic. In 2023 the U.S. General Surgeon declared loneliness a public health concern, with Americans aged 18-34 being more likely to experience these feelings, with 30% of this age group saying they experience feelings of loneliness everyday or several times a week. 

The ventral tegmental area (VTA) contains dopamine-producing neurons that project to various brain regions. It plays crucial roles in reward processing, motivation, learning, memory, and emotional arousal. Abnormalities in VTA function have been associated with addiction and depression. Upregulation of delta opioid receptors in various parts of the brain is related to chronic pain, chronic inflammation, cancer, and early life adversity. Kappa receptors in the VTA play an integral role in stress, drug seeking behavior, mood and reward, as well as addiction. Previous research has stated that chronic consumption of substances of abuse causes indirect upregulation of the κ-receptor/dynorphin system. It also has been previously noted that the opioid system plays an integral role in regulating the need for social interaction.
Design/Methods:
Stress tests were conducted on control (group-housed) and experimental (individually-housed) rats. Behavioral recordings were obtained for analysis, and subjects were euthanized to quantify changes in mu opioid receptor expression in the VTA.
Results:
SI stress induced significant upregulation of delta and kappa opioid receptors in the VTA of experimental rats compared to controls.
Conclusions:
SI caused an upregulation of delta and kappa opioid receptors in the VTA, leading to behavioral changes in where rats were less social and engaged in more active coping mechanisms. SI almost acted as a disease state for single housed rats.
10.1212/WNL.0000000000216132
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