Desensitization and enhancement of neurotensin/neuromedin N mRNA responses in subsets of rat caudate-putamen neurons following multiple administrations of haloperidol

Abstract

Striatal neurons that respond to blockade of dopamine receptors with altered expression of neurotensin/neuromedin N mRNA were examined. Injections of haloperidol were given to rats at four or 24 h and both four and 24 h prior to sacrifice. Pair-matched controls were injected with equivalent volumes of vehicle at either 4 or 24 h prior to sacrifice. Sections of striatum were processed non-isotopically with a cRNA neurotensin/neuromedin N probe. Massive numbers of neurons exhibited hybridization in the lateral and dorsolateral caudate-putamen at 4 h. At 24 h, hybridized neurons were few in lateral and dorsolateral parts of the caudate-putamen, but more numerous in the dorsomedial and ventrolateral caudate-putamen than in controls. A second injection of haloperidol 4 h prior to sacrifice enhanced the dorsomedial/ventrolateral response, but failed to elicit substantial numbers of lateral and dorsolateral hybrids, as were observed at 4 h after one injection. Resistance of neurotensin expression to a second injection of haloperidol was selective for the lateral and dorsolateral parts of the caudate-putamen and may reflect residual blockade by haloperidol or altered DA receptors or second messengers. Sections subjected to immunohistochemical processing for neurotensin peptide and in situ hybridization with the neurotensin/neuromedin N mRNA probe exhibited numerous neurons in the dorsomedial and ventrolateral quadrants of the caudate-putamen that were double-labeled with immunoperoxidase and hybridization signals. This suggests that peptide synthesis, as opposed to decreased release of peptide, has a role in the accumulation of neurotensin immunoreactivity by dorsomedial and ventrolateral striatal neurons.