Rats bred for enhanced apomorphine susceptibility have elevated tyrosine hydroxylase mRNA and dopamine D2-receptor binding sites in nigrostriatal and tuberoinfundibular dopamine systems

Autor: N.Y. Rots, P. Voorn, E.R. de Kloet, William Rostène, Alexander R. Cools, Anne Bérod
Rok vydání: 1996
Předmět:
Male
medicine.medical_specialty
Apomorphine
Tyrosine 3-Monooxygenase
Dopamine
Drug Resistance
Farmacotherapie van psychomotorische ziektebeelden
fundamenteel en toegepast onderzoek
Nigrostriatal pathway
Substantia nigra
Biology
Dopamine agonist
Dopamine receptor D1
Internal medicine
Dopamine receptor D2
medicine
Animals
RNA
Messenger
Rats
Wistar
GeneralLiterature_REFERENCE(e.g.
dictionaries
encyclopedias
glossaries)
Molecular Biology
In Situ Hybridization
Binding Sites
Tyrosine hydroxylase
Receptors
Dopamine D2
Receptors
Dopamine D1
General Neuroscience
Arcuate Nucleus of Hypothalamus
Receptors
Dopamine D3
Pharmacotherapy of psychomotor diseases
fundamental and applied research
Corpus Striatum
Rats
Substantia Nigra
Endocrinology
medicine.anatomical_structure
nervous system
Autoradiography
Neurology (clinical)
Developmental Biology
medicine.drug
Zdroj: Brain Research, 710, 1-2, pp. 189-196
Brain Research, 710, pp. 189-196
Brain Research, 710, 189-196
ISSN: 0006-8993
DOI: 10.1016/0006-8993(95)01379-2
Popis: From a Wistar population two rat lines were generated using as criterion the behavioral response to the dopamine agonist apomorphine. Rats of the apomorphine-susceptible (apo-sus) line revealed a vigorous gnawing response to apomorphine administration while the other rat line, the apomorphine-unsusceptible (apo-unsus) line, was selected for lack of response to the drug. In the present study using the 12th and 13th generation of these genetically selected lines, we have investigated whether this difference in apomorphine responsiveness was correlated with changes in dopamine neurochemistry. Therefore, we measured tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis, as well as dopamine D 1 and D 2 receptor mRNA levels in discrete brain regions by in situ hybridization. Dopamine ( D 2 /D 3 ) receptor binding was assessed with [ 125 I]iodosulpride in a membrane binding assay and by quantitative autoradiography on tissue sections. [ 3 H]SCH 23390 was used to analyze D 1 receptor binding. Apo-sus rats displayed significantly higher TH mRNA levels in the A 9 cell group of the substantia nigra pars compacta and in the A 12 cell group of the arcuate nucleus. No difference was found in the A 10 cell group of the VTA and the A 6 cell group of the locus coeruleus. The density of D 2/3 binding sites as well as D 1 receptor mRNA levels in the striatal projection area of the A 9 substantia nigra neurons, were significantly elevated in apo-sus rats. Dopamine D 2 receptor mRNA and D 1 receptor binding levels in caudate putamen and nucleus accumbens, however, were similar in rats of both lines. In conclusion, high apomorphine susceptibility is related to a potentially enhanced dopamine responsiveness selective for the nigrostriatal and tuberoinfundibular pathways.
Databáze: OpenAIRE
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