Dopaminergic regulation of extrapyramidal and limbic neurotensin activity

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Title Dopaminergic regulation of extrapyramidal and limbic neurotensin activity
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Wagstaff, John David
Date 1995-12
Description The dopaminergic regulation of extrapyramidal and limbic neurotensin (NT) systems was examined by combining in vivo microdialysis with a sensitive radioimmunoassay. Extracellular neurotensin-like immunoreactivity (NTLI) levels were characterized as being of neuronal origin and were compared with tissue NTLI content following the administration of dopaminergic drugs. Dopamine (DA) D-2 receptors oppositely regulated both tissue NTLI content and extracellular NTLI levels in the striatum and nucleus accumbens. An inverse correlation was observed between tissue and extracellular NTLI levels after administration of a D-2 agonist. This treatment decreased tissue NTLI content and increased extracellular NTLI levels in both these regions. Blockade of D-2 receptors increased tissue NTLI content, whereas extracellular levels were diminished. These effects indicate that, in some cases, variations in tissue NTLI content may reflect changes in the release of NT and that D-2 receptors are involved in the basal regulation of NT activity. Activation of DA D-1 receptors increased tissue NTLI levels in whole striatum and nucleus accumbens. Surprisingly, extracellular NTLI levels were also elevated after a similar treatment. However, a distinct anterior/posterior delineation was observed in caudate regions following a single dose of a D-1 agonist. NTLI levels in anterior regions increased but were reduced in posterior areas. Thus, an inverse correlation between changes in NTLI content in the posterior caudate and extracellular NTLI levels occurred after D-1 stimulation. Glutamate N-methyl-D-aspartate receptors were found to mediate the effects of D-1 activation on NT release since blockade of these receptors prevented the D-1 agonist-induced increase in extracellular NTLI levels. Blockade of D-1 receptors did not alter tissue NTLI content or extracellular NTLI levels in the striatum or accumbens, implying that D-1 receptors do not regulate basal NT activity. Endogenous NT systems reduced the DA response to a low dose of methamphetamine (METH). In turn, this dose of METH stimulated NT release in both striatum and nucleus accumbens. Surprisingly, the effects on NT release were diminished with increasing doses of METH. D-2 receptors appeared to regulate the low-dose effect of METH in the accumbens, whereas the coactivation of D-1 and D-2 receptors was necessary in the striatum. These results help to elucidate the physiological relevance of the complex interactions between DA and NT pathways.
Type Text
Publisher University of Utah
Subject Interacions; Endopeptidases
Subject MESH Dopamine; Neurotensin
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Dopaminergic regulation of extrapyramidal and limbic neurotensin activity." Spencer S. Eccles Health Sciences Library. Print version of "Dopaminergic regulation of extrapyramidal and limbic neurotensin activity." available at J. Willard Marriott Library Special Collection. QP6.5 1995 .W33.
Rights Management © John David Wagstaff.
Format application/pdf
Format Medium application/pdf
Format Extent 1,209,963 bytes
Identifier undthes,5101
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship USPHS gtants DA 00869 and DA 09407
Master File Extent 1,209,985 bytes
ARK ark:/87278/s65b0496
Setname ir_etd
ID 191101
Reference URL https://collections.lib.utah.edu/ark:/87278/s65b0496
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