Neurotensin 1 receptor in the prelimbic cortex regulates anxiety-like behavior in rats

The central neurotensin system has been implicated in reward, memory processes, also in the regulation of anxiety. However, the neural substrates where neurotensin acts to regulate anxiety have not been fully identified. The prelimbic region of medial prefrontal cortex (PrL) holds a key position in the modulation of anxiety-related behaviors and expresses neurotensin 1 receptor (NTS1). This study investigated the effects of activation or blockade of NTS1 in the PrL on anxiety-like behaviors of rats. Our results demonstrated that infusion of a selective NTS1 agonist or neurotensin into the PrL produced anxiogenic-like effects. Administration of a NTS1 antagonist into the PrL did not affect anxiety-like behaviors of normal rats, but attenuated anxiogenic effects induced by restraint stress. Moreover, we employed molecular approaches to downregulate the expression of NTS1 in the PrL, and found that downregulation of NTS1 in the PrL induced anxiolytic effects in restraint stress rats, also confirming the pharmacological results. Together, these findings suggest that NTS1 in the PrL is actively involved in the regulation of anxiety.