Work

Antidepressant-like effects of extinction learning as an animal model of behavioral therapy

Year: 2025

Type: article

Abstract: Exposure-based behavioral therapy, the most effective treatment for posttraumatic stress disorder (PTSD), also reduces depressive symptoms. However, neurobiological mechanisms underlying the beneficial effects of exposure-based behavioral therapy on depression remain unknown. Our lab has established fear extinction as a rat model of exposure therapy to investigate the mechanisms underlying its therapeutic behavioral effects in chronically stressed rats. In this study, we demonstrated that extinction learning reduced immobility in the forced-swim test and reversed chronic stress-induced reduction in sucrose preference. Chemogenetic inactivation of pyramidal neurons in the ventral medial prefrontal cortex (vmPFC) prevented these antidepressant-like effects of extinction. Extinction learning enhanced synaptic plasticity, reflected by enhanced optogenetically-induced long-term potentiation of mPFC responses evoked by stimulation of the afferent input from the mediodorsal thalamus (MDT). These results suggest that activity-dependent neuroplasticity induced in vmPFC by extinction learning may contribute to its antidepressant-like effects after chronic stress.

Source: Molecular Psychiatry

DOI: 10.1038/s41380-025-03380-8

Authors: Jing Liu, Sarah E. Bulin, David A. Morilak

Institutions: The University of Texas at San Antonio Health Science Center, South Texas Veterans Health Care System

Language: English

Topic: Memory and Neural Mechanisms

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,490