Neurotensin

Role of central neurotensin in regulating feeding: Implications for the development and treatment of body weight disorders.

Laura E Schroeder, Gina M Leinninger

The peptide neurotensin (Nts) was discovered within the brain over 40years ago and is implicated in regulating analgesia, body temperature, blood pressure, locomotor activity and feeding. Recent evidence suggests, however, that these disparate processes may be controlled via specific populations of Nts neurons and receptors. The neuronal mediators of Nts anorectic action are now beginning to be understood, and, as such, modulating specific Nts pathways might be useful in treating feeding and body weight disorders. This review considers mechanisms through which Nts normally regulates feeding and how disruptions in Nts signaling might contribute to the disordered feeding and body weight of schizophrenia, Parkinson's disease, anorexia nervosa, and obesity. Defining how Nts specifically mediates feeding vs. other aspects of physiology will inform the design of therapeutics that modify body weight without disrupting other important Nts-mediated physiology.

Neurotensin, schizophrenia, and antipsychotic drug action.

Becky Kinkead, Charles B Nemeroff

The search for the underlying pathophysiology of schizophrenia has been an active avenue of investigation since the disease was first recognized more than 100 years ago. Although a great deal of the research has been driven by the known pharmacology of effective antipsychotic drugs, i.e., overactivity of the dopamine system, recent advances in neurobiology provide evidence that reduced synaptic connectivity/neurotransmission may play a substantial role in this disorder. One neuropeptide long posited to play a role in the biology of schizophrenia is neurotensin (NT). Central nervous system administration of NT has been shown to produce a wide variety of effects. Because of its close association with the dopamine (DA) system, the role of the NT system in clinical disorders hypothesized to involve DA circuits such as schizophrenia, Parkinson's disease, and drug abuse has been closely scrutinized. In addition, NT neurotransmission has been implicated in regulation of the stress response, stress-induced gastric ulcers, temperature regulation, food consumption, and analgesia. NT also acts as a growth factor in a variety of human cancer cell lines derived from lung, colon, prostate, and pancreas. This review first provides a background of the NT system. Second, data indicating that NT may mediate the effects of antipsychotic drugs are summarized. Third, data implicating NT in the pathophysiology of schizophrenia are described. Finally, evidence suggesting the use of NTergic compounds as novel antipsychotic drugs are presented.