Early abnormalities of retinal dopamine pathways in rats with hereditary retinal dystrophy.
The dopaminergic pathway that affects rod-driven horizontal cells has been studied in the Royal College of Surgeons (RCS) rat during the period preceding photoreceptor degeneration (postnatal day 17-24). The experiments were performed by intracellular recording from single horizontal cells in vitro. Horizontal cells from the recessive control animals (postnatal day 17-24) were depolarized by dopamine (10 microM) and hyperpolarized by the D1 antagonist SCH 23,390 (10 microM). In contrast, cells from age-matched dystrophic retinas, though depolarized by dopamine, were unaffected by SCH 23390 (10-100 microM), suggesting a significant reduction in the level of endogenous dopamine release. Histologic examination for catecholaminergic neurons revealed no differences in either the cell number or anatomy between the retinas of the control and dystrophic animals. Furthermore, perfusion of the control retinas with melatonin (500 nM-1 microM) yielded response characteristic of the dystrophic type. In the period preceding degeneration, the RCS retina thus displays a discrete abnormality in dopaminergic pathways, such that there is a gross reduction in endogenous dopamine release below that required to activate D1 receptors. Since melatonin levels have been shown to be high in these retinas, we propose that abnormalities in the dopamine-melatonin systems give rise to an electrophysiologic deficit in the postphotoreceptoral retina of the RCS rat.
Hankins
M
M
Gunnar Svaetichin Laboratory, Department of Biology, Imperial College at Silwood Park, Ascot, Berkshire, UK.
Ikeda
H
H
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004594:Electrophysiology; D005456:Fluorescent Dyes; D008550:Melatonin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism*; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D014795:Visual Pathways
D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D005456:Fluorescent Dyes; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D008550:Melatonin; D004298:Dopamine