Brain receptor dynamics in early and adult life stress: Gateways to maladaptive coping strategies

Abstract

Stress plays a significant role in the onset of numerous psychiatric disorders. Depending on individual resilience or stressor's nature, long-term changes to stress in the brain can lead to a wide range of behavioral symptoms, including social withdrawal, feelings of helplessness, and emotional overeating. The brain receptor molecules are key mediators of these processes, translating neuromodulatory signals into neuronal responses or circuit activity changes that ultimately shape behavioral outcomes. Here, I highlight several of my previous studies that reveal the pivotal role of receptor molecules in critical brain regions such as the nucleus accumbens, lateral hypothalamus, and lateral septum. I identified how mGluR5 signaling in the nucleus accumbens promotes stress resilience through pathways involving ΔFosB and SRF, while leptin receptor or glucocorticoid receptor signaling within lateral hypothalamic circuits contributes to stress eating. Additionally, I uncovered the role of dopamine receptor 3 signaling in the lateral septum in mediating the impact of early life stress on social behaviors. These findings underscore the functional relevance of brain receptor molecules in transducing stress—from early life through adulthood—into maladaptive coping behaviors. As druggable targets, these receptor-mediated pathways provide a critical foundation for developing targeted interventions to alleviate stress-related psychiatric symptoms.