beta,beta'-Iminodipropionitrile-induced persistent dyskinetic syndrome in mice is transiently modified by MPTP.
Chronic administration of iminodipropionitrile (IDPN) is known to produce a persistent dyskinetic syndrome. Recent neurochemical reports seem to point out the dopaminergic system as having an important role in mediating IDPN syndrome. In order to identify a possible role for the nigrostriatal dopaminergic pathway in determining at least some aspects of the IDPN-induced dyskinetic syndrome, we used the neurotoxin, 1-methyl, 4-phenyl,1,2,3,6-tetrahydropyridine (MPTP), as a tool for investigating which aspects of the IDPN-related syndrome could be due to enhanced dopaminergic activity in the neostriatum. In mice made permanently dyskinetic with IDPN, MPTP administration produced dramatic and biphasic effects on all behavioral patterns characteristic of the dyskinetic syndrome. Six weeks after the syndrome occurred, IDPN failed to produce any change in striatal DA levels with respect to controls. By contrast, IDPN seems to reduce striatal levels of extraneuronal metabolites of DA. These data suggest that the activity of the nigrostriatal dopaminergic pathway does not play a leading role in the maintenance of IDPN-related syndrome. The transient modification of all behavioral parameters immediately after MPTP administration could be explained by acute effects of MPTP on other dopaminergic areas which are not permanently lesioned by this neurotoxin, or by the acute effects of MPTP on the release of other neurotransmitters.
Fornai
F
F
Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Alessandri
M G
MG
Saginario
A
A
Vaglini
F
F
Corsini
G U
GU
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D015259:Dopamine Agents / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D015306:Biogenic Monoamines; D015259:Dopamine Agents; D009570:Nitriles; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; C008110:3,3'-iminodipropionitrile; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid