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Huntington chorea is not associated with hyperactivity of nigrostriatal dopaminergic neurons

Studies in postmortem tissues and in rats with kainic acid lesions

Laboratory of Clinical Neurochemistry. Department of Neurology (Dr. Melamed). Hadassah University Hospital. Jerusalem, Israel, Laboratory of Neuroendocrine Regulation, Massachusetts Institute of Technology. (Drs. Melamed and Hefti) Cambridge. MA, and the Department of Neurology-Neuropathology, Harvard Medical School, McLean Hospital, Belmont. MA (Dr. Bird)

We estimated dopamine release postmortem in the neostriatum of patients with Huntington disease (HD) and in controls. In HD, dopamine levels were unchanged in caudate and elevated in putamen, but homovanillic acid (HVA) and the ratio HVA:dopamine were unaltered in both nuclei. When rats were injected with kainic acid (an experimental model of HD), dopamine levels in striatum remained unchanged 2 to 30 days postoperatively; HVA and 3,4,-dihydroxyphenylacetic acid (DOPAC) increased significantly from 2 to 18 days after injections but returned to normal levels later. These findings suggest that the nigrostriatal projection adapts to loss of striatal neurons that normally influence dopamine release and is not hyperactive in HD chorea.

Address correspondence and reprint requests to Dr. Melamed. Department of Neurology, Hadassah University Hospital, Jerusalem, P.O.B. 12 000, Israel.

Supported, in part, by a grant donated by the Wars chaw family in honor of Lawrence A. Harvey and by a U.S.A.-Israel Binational Science Foundation Grant No. 2348.

Presented in part at the thirty-third annual meeting of the American Academy of Neurology, Toronto, Canada, April 1981

Accepted for publication October 19, 1981

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