Excessive bracing reactions and their control by atropine and l-DOPA in an animal analog of parkinsonism

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Abstract

If suddenly pushed forward or backward while standing, many people with parkinsonism brace rigidly without stepping, or with short shuffling steps which are unable to counteract their fall, and they must be caught or they will fall to the floor. In an animal analog of this parkinsonian symptom, we used the rat made akinetic through intraventricular application of 6-hydroxydopamine, which severely depletes brain catecholamines. The hindquarters were lifted off the ground so that the animal was standing on its forelegs. Such a rat shows parkinsonian-like bracing instead of stepping when it is suddenly pushed forward in wheelbarrow-like fashion and moved along a smooth surface at a moderate speed. Atropine sulfate, an anticholinergic drug, helps to alleviate the bracing reaction so that the animal steps with its forelegs. l-DOPA also is useful for counteracting bracing, and is more effective than atropine when the animal is pushed along at higher speeds, which require longer, more rapid steps. However, because l-DOPA often produces circling in 6-hydroxydopamine-treated rats, it was administered together with atropine sulfate to yield more effective forward stepping. We regard the Parkinson-like bracing reactions and akinesia not simply as bizarre abnormalities but as normal elements of a subsystem that is organized to maintain static, stable support. We suggest that severe catecholamine deficiency leaves this subsystem virtually intact while simultaneously suppressing other subsystems such as those involved in dynamic locomotion. The action of atropine and l-DOPA may be considered in terms of how they may affect the balance of these subsystems.

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    This study was supported by National Research Council of Canada grant A8273 to Dr. Whishaw, National Institutes of Health grant R01 NS 11671, University of Illinois Biomedical Research grant, a William T. Grant Foundation grant to Dr. Teitelbaum, and a University of Illinois Biomedical Research grant to Dr. Ramirez. We are grateful to Dr. Lucien Coté and Dr. Stanley Fahn of the Columbia University Medical School Neurology Department, to Dr. Roger Duvoisin of Mt. Sinai Medical School Neurology Department in New York, and to Dr. John Helfrich, Christie Clinic, Champaign, Illinois for allowing us to observe some of their patients. We also thank Dr. Coté and Dr. Fahn for their comments on the manuscript. We thank Hoffman-La Roche, Inc. of Nutley, New Jersey, for sending us a sample of R-factor. We thank Nancy Peshkin for technical assistance and Debie Kassner-Whelchel for typing the manuscript.

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