Neurotensin receptors as modulators of glutamatergic transmission.

Functional studies have provided evidence supporting the concept that the tridecapeptide neurotensin (NT) acts in the central nervous system as a classical neurotransmitter and/or as an important modulator of neuronal signalling. The role of NT in the regulation of the striatal amino acidergic transmission, mainly by antagonising D2 receptor function, will be analysed. In addition, in different rat brain regions, including the basal ganglia, the contribution of NT receptors in modulating and reinforcing glutamate signalling will be shown including the involvement of interactions between NT and NMDA receptors. Since the enhancement of glutamate transmission and in particular the excessive activation of NMDA receptors, has been postulated to be an important factor in the induction of glutamate-mediated neuronal damage, the involvement of NT in the glutamate-induced neurodegenerative effects will be discussed. Moving from these observations and in order to further investigate this issue, results from preliminary behavioural, functional and biochemical experiments will be presented on the putative neuroprotective effect obtained by the blockade of NT receptor 1 (NTS1) via the systemic administration of the selective NTS1 antagonist SR48692 in an in vivo animal model of Parkinson's disease [unilateral nigral 6-hydroxydopamine (6-OHDA) induced lesion of the nigrostriatal pathway].