Interactions of neurotensin with dopamine-containing neurons in the central nervous system.

1. Neurotensin (NT) is a tridecapeptide that fulfills many of the requisite criteria for neurotransmitter status in the mammalian central nervous system. 2. Neuroanatomical studies have revealed that DA and NT neurons are proximal in several limbic areas and that NT receptors are present on both DA perikarya and certain DA nerve terminals. 3. When injected intraventricularly or directly into the nucleus accumbens (ACC), NT produces effects similar to antipsychotic drugs, e.g. blockade of the hyperactivity produced by d-amphetamine or cocaine. 4. Chronic administration of antipsychotic drugs such as haloperidol produces increases in NT concentration in the ACC and caudate nucleus. Atypical antipsychotic drugs produce increases in NT concentration only in the ACC. 5. In certain drug-free schizophrenic patients, the concentration of NT in cerebrospinal fluid is reduced. 6. It appears that NT may modulate the activity of DA neurons in the mesolimbicocortical DA system.