Augmented sensitivity of D1-dopamine receptors in lateral but not medial striatum after 6-hydroxydopamine-induced lesions in the neonatal rat
| Autor: | P E, Simson, K B, Johnson, H A, Jurevics, H E, Criswell, T C, Napier, G E, Duncan, R A, Mueller, G R, Breese |
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| Rok vydání: | 1992 |
| Předmět: |
Tyrosine 3-Monooxygenase
Receptors Dopamine D1 Corpus Striatum Nucleus Accumbens Rats Levodopa Rats Sprague-Dawley Animals Newborn Pregnancy Animals Autoradiography Female 2 3 4 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine Guanosine Triphosphate Oxidopamine Proto-Oncogene Proteins c-fos Adenylyl Cyclases |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 263(3) |
| ISSN: | 0022-3565 |
| Popis: | Lesioning of neonatal rats with the neurotoxin 6-hydroxydopamine (6-OHDA) reduced striatal dopamine (DA) levels to 3% of control levels and produced marked increases in the behavioral effects of the selective D1-DA receptor agonist SKF-38393 in these animals when tested as adults. However, no differences were observed, either in basal or D1-DA-stimulated striatal cAMP formation or in forskolin-stimulated or GTP-stimulated cAMP production, between control and lesioned animals. C-fos-like immunoreactivity after SKF-38393 was significantly greater in dorsolateral vs. ventromedial aspects of the striatum in lesioned animals. Like the c-fos response, augmented electrophysiological responsiveness to SKF-38393 occurred in lesioned rats in lateral, but not medial, portions of the striatum. No differences were found in nucleus accumbens in sensitivity to SKF-38393 between control and lesioned rats. Although autoradiographic determination of D1-DA receptor binding throughout the striatum and nucleus accumbens revealed no differences between unlesioned and lesioned rats, tyrosine hydroxylase-like immunoreactivity was reduced with a regional distribution inversely related to c-fos-like immunohistochemical expression. These findings demonstrate that regionally enhanced electrophysiological sensitivity of striatal neurons to D1-DA receptor agonists after neonatal 6-OHDA-induced lesions is associated with regional changes in c-fos-like immunoreactivity and tyrosine hydroxylase-like immunohistochemistry, but not with changes in D1-DA receptor autoradiography or D1-DA-stimulated adenylyl cyclase activity. Such regional consequences of 6-OHDA-induced lesions in neonates may contribute to the unique behavioral patterns observed when these rats are challenged with L-dopa or D1-DA agonists as adults. |
| Databáze: | OpenAIRE |
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