Neonatal 6-hydroxydopamine lesions lead to opposing changes in the levels of dopamine receptors and their messenger RNAs

• Published in: Neuroscience 1995-09, Vol.68 (2), p.505-518
• Main Authors: Frohna, P.A., Neal-Beliveau, B.S., Joyce, J.N.
• Format: Article
• Language: English
• Subjects: Aging - physiology; Animals; Animals, Newborn - metabolism; Autoradiography; Biological and medical sciences; Development. Senescence. Regeneration. Transplantation; Dopamine - metabolism; Dopamine - physiology; Fundamental and applied biological sciences. Psychology; In Situ Hybridization; Neostriatum - drug effects; Neostriatum - growth & development; Neostriatum - metabolism; Oxidopamine - toxicity; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - biosynthesis; Receptors, Dopamine D1 - drug effects; Receptors, Dopamine D2 - biosynthesis; Receptors, Dopamine D2 - drug effects; RNA, Messenger - biosynthesis; Substantia Nigra - drug effects; Substantia Nigra - growth & development; Substantia Nigra - metabolism; Sulfur Radioisotopes; Sympatholytics - toxicity; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(95)00155-C

Previous studies have established that selective damage to the early-developing components of the mesostriatal dopamine system produces profound changes in dopamine D 1 receptor-mediated behaviors, while decreasing D 1 receptor density. In order to better understand the effects of early intrastriatal 6-hydroxydopamine lesions, we studied the ontogenetic expression (postnatal days 7, 14, 35 and 90) of D 1 and D 2 receptors, and their corresponding messenger RNAs, in rats that had received intrastriatal 6-hydroxydopamine or vehicle lesions on postnatal day 1. Using receptor autoradiography, significant ( P < 0.05) decreases in [ 3H]SCH 23390 binding to D 1 receptors in the rostral and caudal dorsomedial and ventromedial caudate of 6-hydroxydopamine-lesioned animals were evident by postnatal day 7, and remained depressed at all future time points. A significant decrease in D 1 receptor concentration occurred in the dorsolateral caudate at later time points (postnatal days 35 and 90). [ 3H]Spiperone binding to D 2 receptor sites was unchanged throughout the entire study. In situ hybridization for D 1 and D 2 messenger RNA expression showed contrasting results. 6-Hydroxydopamine induced significant decreases of D 1 messenger RNA levels in the dorsolateral and dorsomedial caudate by postnatal day 7. By postnatal day 14, messenger RNA expression was significantly elevated in the dorsomedial and ventromedial caudate of the 6-hydroxydopamine group, and remained elevated thereafter. D 1 messenger RNA levels became elevated in the lateral caudate at later time points (postnatal days 35 and 90). The opposing changes in D 1 receptor concentrations and the messenger RNA encoding the protein did not occur as a consequence of increased transport of D 1 receptors to striatonigral terminals. D 2 messenger RNA levels in the dorsal caudate were significantly decreased on postnatal day 7, and became higher than controls at postnatal day 14, but were unchanged from controls at later time points. Together, the D 1 receptor and D 1 messenger RNA findings suggest that the normal relationship between levels of D 1 receptor transcript and D 1 receptor protein is permanently altered following the early loss of dopamine. In contrast, the results indicate that dopamine plays a minor role in the early postnatal development of the D 2 receptor protein and transcript. These findings suggest that dopamine may be involved in the coordinated expression of some dopamine receptors and their co