Neurotensin modulates dopamine neurotransmission at several levels along brain dopaminergic pathways

Neurotensin is a tridecapeptide that was isolated 15 years ago from bovine hypothalamus and, since then, has been shown to fulfill the major criteria that define a neurotransmitter/neuromodulator. There is considerable evidence that neurotensin interacts with mesencephalic dopamine systems. Anatomical and functional data indicate that neurotensin modulates dopamine neurotransmission at all levels along nigrostriatal and mesolimbic dopamine pathways. The peptide appears to functionally antagonize the effects that the amine exerts via both presynaptic (auto) and postsynaptic dopamine receptors. This confers a neuroleptic-like pharmacological profile to neurotensin. In addition, extensive neurotensin/dopamine colocalization occurs in a subpopulation of mesencephalic dopamine neurons that project to the prefrontal cortex. Recently, the neurotensin precursor has been shown to contain another neurotensin-like peptide, neuromedin N, that binds with high affinity to brain neurotensin receptors and displays some neuroleptic-like effects. Therefore, neuromedin N may be considered as a potential comodulator (with neurotensin) of dopamine functions. Given the implications of dopamine systems in certain neuropathological and psychotic disorders such as Parkinson's disease and schizophrenia it is likely, as already suggested by some experimental evidence, that neurotensin plays an important role in the etiology and pathogenesis of these diseases.