Neurotensin and Neurotensin Receptors in Stress-related Disorders

Neurotensin is a 13-amino acid neuropeptide widely distributed in the CNS that has been involved in the pathophysiology of many neural and psychiatric disorders.  Three neurotensin receptors (NTSRs) form the neurotensinergic system.  NTSR1 is the main mediator of neurotensin, displaying effects in both the CNS and the periphery, while NTSR2 is mainly expressed in the brain, and NTSR3 has a broad expression pattern.  Stress responses and anxiety involve mainly NTSR1, but also NTSR2 and NTSR3.  NTSR1 and NTSR3 are primarily implicated in depression, while NTSR2 and secondarily NTSR1 in post-traumatic stress disorder (PTSD).   NTSR1 is associated with substance and drug abuse and NTSR2 with fear memory, while all NTSRs seem to be implicated in ethanol consumption.  Some of the actions of neurotensin and NTSRs in these pathological settings may be driven through interactions between neurotensin and corticotrophin releasing factor.

In a recent, review, Kyriatzis and colleagues bring together up-to-date studies showing an involvement of the neurotensinergic system in different aspects of the stress response and the main stress-related disorders, such as depression and anxiety, PTSD and associated symptoms, ethanol addiction and substance abuse, with emphasis on gene, mRNA, and protein alterations of neurotensin and NTSRs.  Behavioural and pharmacological studies lead to evidence-based suggestions on the implicated regulating mechanisms.

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