Central and peripheral effects of iminodipropionitrile on catecholamine metabolism in rats.
Chronic treatment with iminodipropionitrile (IDPN) causes a behavioral syndrome characterized by lateral and vertical neck dyskinesias, hyperactivity, random circling, and increased startle response (the "ECC syndrome"). The effects of the neurotoxin on norepinephrine (NE), dopamine (DA), and their metabolites were evaluated in the hypothalamus and the striatum of IDPN-treated animals. Urinary excretion of the amines was also measured. There was no significant persistent change in central metabolism of dopamine. There was a transient increase in NE metabolism in the hypothalamus after the third injection of IDPN that lasted until the development of the syndrome at 7 days of drug treatment. Urinary excretion of NE and its metabolites was increased on the day that the syndrome developed. Urinary excretion of homovanillic acid was persistently decreased throughout and after cessation of drug treatment. There was no change in the excretion of either dopamine or dihydroxyphenyl acetic acid. The ratio of total NE/total DA excreted by IDPN-treated rats was the inverse of that of control animals. These results suggest that persistent dyskinesias may be associated with a relative increase in facilitatory NE-dependent mechanisms at the cortical, subcortical, or spinal cord level.
Cadet
J L
JL
Neuropsychiatry Branch, St. Elizabeth's Hospital, Washington, D.C. 20032.
Karoum
F
F
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000652:urine; D006719:Homovanillic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains
D009570:Nitriles; D015102:3,4-Dihydroxyphenylacetic Acid; C008110:3,3'-iminodipropionitrile; D008734:Methoxyhydroxyphenylglycol; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid