The present study was aimed at determining the extent to which excitotoxic lesions of the medial prefrontal cortex reduce neurotensin receptors within the striatum, the nucleus accumbens, the ventral tegmental area and the substantia nigra. The medial prefrontal cortex was unilaterally lesioned with ibotenic acid and 10 days later brain sections were processed for neurotensin receptor autoradiographic analysis using 0.1 nM [(125)I-Tyr3]neurotensin with, or without, levocabastine. Analysis revealed at least two sites, one levocabastine-insensitive neurotensin NT(1) and one levocabastine-sensitive neurotensin NT(2)-like. The proportion of the latter site was high within the caudal striatum, the nucleus accumbens and the medial prefrontal cortex. Lesions produced a 60% to 80% reduction in neurotensin NT(1) within the ipsilateral medial prefrontal cortex, but no change in the sub-cortical nuclei. An increase in neurotensin NT(2)-like receptors was found in ipsilateral dorso-caudal caudate. These results show that a significant amount of neurotensin NT(1) receptors are located on neurons within the medial prefrontal cortex but not on their efferent terminals.