Neurotensin-dopamine interactions: Relevance to schizophrenia and the action of antipsychotic drugs

Despite the considerable data generated thus far, a unifying theory for the role(s) of NT in the CNS has not been achieved. However, several conclusions with clinical relevance can be made about neurotensin. First, NT is intimately associated with the mesolimbic DA system and has the ability to selectively modulate this system. Second, NT possesses a pharmacobehavioral profile that is similar to antipsychotic drugs, with many similarities to the atypical class of antipsychotics drugs. If the pathogenesis of schizophrenia is related to dopaminergic hyperactivity, then the existence of an endogenous NT system that modulates the activity of the DA system, may represent a mechanism for the prevention of psychosis. The ability of the atypical antipsychotic drugs to effectively reduce the symptoms of schizophrenia does not depend entirely upon the blockade of D2 receptors, yet many of these drugs alter NT concentrations. The development of NT receptor agonists that can cross the blood brain barrier may prove valuable in the treatment of schizophrenia, while avoiding the liability of EPS and TD.