BLOCKADE OF NEUROTENSIN RECEPTORS BY THE ANTAGONIST SR-48692 PARTIALLY PREVENTS RETROGRADE AXONAL-TRANSPORT OF NEUROTENSIN IN RAT NIGROSTRIATAL SYSTEM

The effect of SR 48692, a potent and selective non-peptide antagonist of the neurotensin receptor, was investigated on the retrograde axonal transport of neurotensin in the rat nigrostriatal dopamine pathway. W hen rats were injected in the striatum with (3-[I-125]iodotyrosyl(3))n eurotensin, a substantial accumulation of radioactivity appeared in th e ipsilateral substantia nigra 1.5 h after injection, and highest leve ls (336 +/- 23 dpm/mg of protein) were observed 2.5-3.5 h after the in jection. The phenomenon required a pretreatment of the animals with th iorphan (30 mu g) an inhibitor of endopeptidase. The amount of radioac tivity accumulated (3.5 h) was found to be reduced (25%) by local (100 nM) or peripheral administration of SR 48692 (5, 10, 20 mg/kg, i.p.; 25%, 40%, 40%, respectively). Our results indicate that blockade of ne urotensin receptors by a selective non-peptide receptor antagonist aff ects the retrograde axonal transport of the tridecapeptide, and furthe r suggest the notion that this process involves neurotensin receptors.