5-hydroxytryptamine type-3A receptor in the process of fear extinction

The 5-hydroxytryptamine type-3 (5-HT3) receptor is the only ionotropic receptor in the family of 5-HT receptors. The 5-HT3 receptor is expressed in limbic regions, such as hippocampus, amygdala and cortex. However, it is not known whether it has a role in fear memory processes. We performed behavioral analyses of 5-HT3A receptor knockout mice in fear conditioning paradigms, and revealed that the 5-HT3A receptor is not required for the acquisition or retention of fear memory but is essential for the extinction of learned fear. Furthermore, we found that the 5-HT3A receptor contributes to the context-specificity of extinction processes. Our results suggest that the 5-HT3A receptor could be a key molecule for regulation of fear extinction, and potentially important therapeutic target for disorders of regulation in fear systems, such as post-traumatic stress-disorder (PTSD).