DESENSITIZATION AND ENHANCEMENT OF NEUROTENSIN NEUROMEDIN-N MESSENGER-RNA RESPONSES IN SUBSETS OF RAT CAUDATE-PUTAMEN NEURONS FOLLOWING MULTIPLE ADMINISTRATIONS OF HALOPERIDOL/

Striatal neurons that respond to blockade of dopamine receptors with a ltered expression of neurotensin/neuromedin N mRNA were examined. Inje ctions 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 neur otensin/neuromedin N probe. Massive numbers of neurons exhibited hybri dization in the lateral and dorsolateral caudate-putamen at 4 h. At 24 h, hybridized neurons were few in lateral and dorsolateral parts of t he caudate-putamen, but more numerous in the dorsomedial and ventrolat eral caudate-putamen than in controls. A second injection of haloperid ol 4 h prior to sacrifice enhanced the dorsomedial/ventrolateral respo nse, but failed to elicit substantial numbers of lateral and dorsolate ral hybrids, as were observed at 4 h after one injection. Resistance o f neurotensin expression to a second injection of haloperidol was sele ctive for the lateral and dorsolateral parts of the caudate-putamen an d may reflect residual blockade by haloperidol or altered DA receptors or second messengers. Sections subjected to immunohistochemical proce ssing for neurotensin peptide and in situ hybridization with the neuro tensin/neuromedin N mRNA probe exhibited numerous neurons in the dorso medial and ventrolateral quadrants of the caudate-putamen that were do uble-labeled with immunoperoxidase and hybridization signals. This sug gests that peptide synthesis, as opposed to decreased release of pepti de, has a role in the accumulation of neurotensin immunoreactivity by dorsomedial and ventrolateral striatal neurons. (C) 1998 Elsevier Scie nce B.V. All rights reserved.