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Dopamine D3 Receptor Mediates Preadolescent Stress-Induced Adult Psychiatric Disorders
Joon H Seo1, Eldo V Kuzhikandathil1
1Department of Pharmacology, Physiology and Neurosciences, Rutgers-New Jersey Medical School, Newark, NJ, 07103, United States of America.
Plos One
|December 1, 2015
Summary
Childhood stress increases adult depression and anxiety. The dopamine D3 receptor plays a key role, with its function altered by stress, suggesting it as a therapeutic target.
Area of Science:
- Neuroscience
- Psychiatry
- Endocrinology
Background:
- Childhood stress is linked to adult depression and anxiety disorders.
- The specific neurobiological mechanisms underlying this link remain unclear.
- The dopamine D3 receptor's role in stress-related behaviors is not fully understood.
Purpose of the Study:
- To investigate the role of the dopamine D3 receptor in the development of anxiety- and depression-related behaviors following adolescent stress.
- To examine sex-specific effects of early-life stress on dopamine D3 receptor function and behavior in adulthood.
Main Methods:
- Preadolescent mice (drd3-EGFP and drd3-null) underwent restraint stress followed by social isolation.
- Adult behavioral assessments included locomotor activity and the Porsolt Forced Swim test.
- Dopamine D3 receptor expression and function were measured in limbic areas (amygdala, hippocampus, nucleus accumbens).
Main Results:
- Preadolescent stress induced anxiety- and depression-related behaviors in adult males, and depression-related behaviors in adult females.
- These stress-induced behaviors were blocked by a D3 receptor antagonist and absent in D3 receptor null mice.
- Sex-specific alterations in D3 receptor expression were observed: males showed decreased amygdala expression, while females showed increased nucleus accumbens expression.
Conclusions:
- The dopamine D3 receptor is critically involved in the development of adult psychiatric disorders resulting from childhood stress.
- Targeting the dopamine D3 receptor may offer a therapeutic strategy for stress-induced mood and anxiety disorders.
- Early-life stress leads to distinct, sex-dependent alterations in dopamine D3 receptor function in the brain.
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