Chronic Administration of Haloperidol Accelerates the Metabolic Rate of Enkephalins in Rat Striatum

Hong, Joo-Heon; Yang, Hongyan; Fratta, Walter; DiGiulio, Anna Maria; Gillin, J. Christian; Costa, E.

doi:10.1016/b978-0-08-023768-8.51449-3

Cited by 2 publications

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“…This is not surprising considering the evidence for direct catecholaminergic innervation of SP and Enk neurons in the CP (46,47). Chronic neuroleptics have been shown to decrease SP and increase Enk levels in the CP (22,23,25,27 …”

Section: Discussionmentioning

confidence: 94%

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Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

Young¹,

Bonner²,

Brann³

1986

Proc. Natl. Acad. Sci. U.S.A.

571

230

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We used in situ hybridization histochemistry with synthetic oligodeoxyribonucleotide probes to identify cells that synthesize mRNAs encoding tyrosine hydroxylase in the mesencephalon and substance P, enkephalin, and dynorphin in the rat forebrain. Dopaminergic cells in the mesencephalon project to the forebrain and influence neuropeptide levels. We examined the effect of unilateral 6-hydroxydopamine lesions (which eliminated tyrosine hydroxylase mRNA-containing cells in the mesencephalon) on substance P, enkephalin, and dynorphin mRNA levels. Substance P mRNA levels were depressed, whereas enkephalin mRNA levels were elevated in consecutive sections from striatal areas in all animals. The effects of the lesions on dynorphin mRNA levels were less robust, and considerable variation between animals was observed. Changes were evident in the levels of message in individual cells but not in the numbers of labeled cells. These effects were not uniform throughout the dopamine-innervated areas, suggesting degrees of control not apparent with RNA blot-hybridization or dotblot analyses.Dopamine is a principal transmitter of the mesostriatal and mesocortical (or mesolimbic) components of the mesencephalic pathways to the forebrain (1), which exert major influences on an animal's behavior. In rats, lesions of these pathways may lead to behavioral deficits, such as akinesia, adipsia, and aphagia, while stimulation leads to increased motor activity and stereotyped behaviors such as sniffing, licking, and gnawing (2, 3). Side effects of neuroleptics such as acute dystonia and tardive dyskinesia and neurological diseases such as Parkinson's disease, in which a deficiency in mesostriatal dopamine is accompanied by movement disorders such as bradykinesia and tremor, demonstrate the importance of dopamine in human motor control (4).Undoubtedly, dopamine, in part, exerts its influence and is influenced in turn by neuropeptide transmitter systems. Extensive evidence exists for complex topographical relationships between these systems in the basal ganglia (5-9). Broadly, the caudate-putamen (CP) system receives input from the substantia nigra (SN) and ventral tegmental area (VTA), while the nucleus accumbens (NA) and olfactory tubercle (OT) are primarily innervated by the VTA. However, there is some overlap in the innervations of these striatal areas by the SN and VTA. Also, the dopamine cell group A8 projects to the NA and ventral CP. These dopamine-innervated areas contain substance P (SP) (10), enkephalin (Enk) (ref. 11 and references within), and dynorphin (Dyn) (12, 13) cell bodies, which project in characteristic ways out of the striatum. In the rat, SP (14-16) and Dyn (17) cells project principally to the SN, especially the pars reticulata, whereas Enk cells project to the globus pallidus (18-21).Changes in striatal neuropeptide biosynthesis result from lesioning mesencephalic dopamine neurons with 6-hydroxydopamine or chronic administration of neuroleptics. SP and SP mRNA levels in the striatum are depressed by neurole...

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Section: Discussionmentioning

confidence: 94%

“…SP and SP mRNA levels in the striatum are depressed by neuroleptics (22)(23)(24). Conversely, Enk levels, Enk synthesis, and Enk mRNA levels are all increased by 6-hydroxydopamine lesions or neuroleptics (25)(26)(27)(28)(29)(30). The effects on Dyn biosynthesis are uncertain (31,32).…”

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confidence: 89%

Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

Young¹,

Bonner²,

Brann³

1986

Proc. Natl. Acad. Sci. U.S.A.

571

230

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“…Unfortunately the specificity and resolution of immunohistochemical methods does not allow one to decide whether or not the two pentapeptides are located in different neuronal pathways and whether the calf brain contains more LE-neurones (Elde, Hokfelt, Johansson & Terenius, 1976;Watson, Akil, Sullivan & Barchase, 1977;Simantov, Kuhar, Uhl & Snyder, 1977b). Previous work from this laboratory has shown that in every structure of the rat brain there is 5 to 10 fold more ME than LE and that when the ME content of specific brain regions increases, as a result of a drug treatment, there is a parallel selective increase of LE, as if the regulation of the two compounds is closely related (Yang, Hong & Costa, 1977;Hong, Yang, Fratta & Costa, 1978a;Gillin, Hong, Yang & Costa, 1978;Hong, Yang, Gillin, Di Giulio, Fratta & Costa, 1978b). We have also observed that ME cross reacts by roughly 10% with LE antiserum.…”

Section: Introductionmentioning

confidence: 99%

ON THE DISTRIBUTION OF [MET⁵]‐ AND [LEU⁵]‐ENKEPHALINS IN THE BRAIN OF THE RAT, GUINEA‐PIG AND CALF

Giulio

Majane

Yang

1979

British J Pharmacology

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1By means of a highly sensitive radioimmunoassay, the content of [met5]-enkephalin (ME) and [leu5]-enkephalin (LE) was measured in various regions of the rat, guinea-pig and calf brain. Provisions were made to differentiate ME from LE by the use of cyanogen bromide (CNBr) to destroy methionine, the carboxy terminal amino acid in the ME sequence. This allows for correction of possible errors due to the cross-reactivity of the ME to the LE antiserum. Evidence is presented to demonstrate that the specific radioimmunoassay combined with the CNBr technique is a valid method to measure LE and ME content in crude tissue extracts. 2 In all the species studied, enkephalins appeared to be highly concentrated in the striatum and hypothalamus while very low amounts were found in the cerebellum and hippocampus. 3 Although the ratio between ME and LE content varied from area to area, the ME content in every region of the rat, guinea-pig and calf brain was more than 4 fold greater than that of LE.

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Chronic Administration of Haloperidol Accelerates the Metabolic Rate of Enkephalins in Rat Striatum

Cited by 2 publications

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Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

ON THE DISTRIBUTION OF [MET⁵]‐ AND [LEU⁵]‐ENKEPHALINS IN THE BRAIN OF THE RAT, GUINEA‐PIG AND CALF

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Chronic Administration of Haloperidol Accelerates the Metabolic Rate of Enkephalins in Rat Striatum

Cited by 2 publications

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Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain.

ON THE DISTRIBUTION OF [MET5]‐ AND [LEU5]‐ENKEPHALINS IN THE BRAIN OF THE RAT, GUINEA‐PIG AND CALF

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ON THE DISTRIBUTION OF [MET⁵]‐ AND [LEU⁵]‐ENKEPHALINS IN THE BRAIN OF THE RAT, GUINEA‐PIG AND CALF