The protein synthesis inhibitor, anisomycin, causes exacerbation of the iminodipropionitrile-induced spasmodic dyskinetic syndrome in rats.
The effects of anisomycin on dyskinetic head movements, circling, and locomotor activity were investigated in the IDPN-induced syndrome. Intracerebroventricular (ICV) injections of anisomycin in conjunction with IDPN caused exacerbation of all aspects of the syndrome, although circling and vertical head dyskinesias (retrocollis) were the most affected. Animals treated with only anisomycin showed persistent retrocollis but not laterocollis or circling. Biochemical studies confirmed the increases in the concentration of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) previously observed in the striata of IDPN-treated rats two weeks after stopping administration of the drug. Rats treated with anisomycin alone also showed significant increases in striatal 5-HT and 5-HIAA concentrations which were somewhat higher on the side of the ICV infusions. Coadministration of IDPN and anisomycin did not cause any further increases in 5-HT or 5-HIAA. These results suggest that inhibition of protein synthesis by IDPN may be one of the processes involved in the development of the persistent dyskinetic syndrome.
Stennett
R
R
Neurological Institute, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
Katz
M
M
Jackson-Lewis
V
V
Fahn
S
S
Cadet
J L
JL
D000818:Animals; D000841:Anisomycin / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000032:analysis / Q000378:metabolism*; D004347:Drug Interactions; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009570:Nitriles / Q000009:adverse effects; D011500:Protein Synthesis Inhibitors; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors
D009570:Nitriles; D011500:Protein Synthesis Inhibitors; D011759:Pyrrolidines; D012701:Serotonin; C008110:3,3'-iminodipropionitrile; D006897:Hydroxyindoleacetic Acid; D000841:Anisomycin