title: 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.
authors.affiliation: Departments of Anatomy and Neurobiology, St. Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA. zahmds@wpogate.slu.edu
authors.forename: D S
authors.initials: DS
authors.lastname: Zahm
authors.forename: E S
authors.initials: ES
authors.lastname: Williams
authors.forename: J E
authors.initials: JE
authors.lastname: Krause
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D017072:Neostriatum / Q000737:chemistry* / Q000166:cytology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009496:Neurotensin / Q000235:genetics*; D010446:Peptide Fragments / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D010446:Peptide Fragments; D012333:RNA, Messenger; C042090:neuromedin N; D009496:Neurotensin; D006220:Haloperidol; D004298:Dopamine