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. When rats were injected in the striatum with (3-[ 125 I]iodotyrosyl 3 )neurotensin, a substantial accumulation of radioactivity appeared in the ipsilateral substantia nigra 1.5 h after injection, and highest levels (336 ± 23 dpm/mg of protein) were observed 2.5–3.5 h after the injection. The phenomenon required a pretreatment of the animals with thiorphan (30 μg) an inhibitor of endopeptidase. The amount of radioactivity 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 neurotensin receptors by a selective non-peptide receptor antagonist affects the retrograde axonal transport of the tridecapeptide, and further suggest the notion that this process involves neurotensin receptors.