Relevance of Dopamine D2/Neurotensin NTS1 and NMDA/Neurotensin NTS1 Receptor Interaction in Psychiatric and Neurodegenerative Disorders

S.      Tanganelli; T.      Antonelli; M.      C. Tomasini; S.      Beggiato; K.      Fuxe; L.      Ferraro

Abstract

The existence of functional NT/dopamine interactions in the central nervous system has been extensively documented. Among others, a possible molecular mechanism underlying the NT-induced modulation of dopamine release is a direct antagonistic NTS1/D2 receptor interaction. More recently, neurochemical experiments also supported the existence of a possible interaction between NT and N-methyl-d-aspartate (NMDA) receptors. In particular, it has been suggested that NT, by amplifying NMDA receptor signaling, could be involved in neurodegeneration.

The present article attempts to provide a summary of current knowledge, mainly emerging from our studies, on the existence of receptor-receptor interactions between NT receptor subtype 1 (NTS1) and dopamine D2 or NMDA receptors in the brain. Special emphasis is placed on the pre and post-synaptic neurochemical mechanisms possibly underlying the involvement of these interactions in the physiopathology of schizophrenia and acute neurodegenerative disorders.

Keywords: Neurotensin analogues, SR48692, NTS1 receptor, Antipsychotic drugs, Dopamine, Receptor heteromers, Microdialysis, Nucleus accumbens, Cerebral ischemia, Glutamate, Structure-activity relationship