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beta,beta'-Iminodipropionitrile-induced persistent dyskinetic syndrome in mice is transiently modified by MPTP
F Fornai1, M G Alessandri, A Saginario
1Institute of Pharmacology, School of Medicine, University of Pisa, Italy.
Abstract:
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.
Insights
Chronic iminodipropionitrile (IDPN) causes persistent dyskinetic syndrome. Neurotoxin MPTP
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Chronic iminodipropionitrile (IDPN) administration induces a persistent dyskinetic syndrome.
- The dopaminergic system is implicated in mediating IDPN-induced syndromes.
- The nigrostriatal dopaminergic pathway's role in IDPN syndrome requires clarification.
Purpose of the Study:
- To investigate the role of the nigrostriatal dopaminergic pathway in IDPN-induced dyskinetic syndrome.
- To determine if enhanced dopaminergic activity in the neostriatum contributes to IDPN syndrome aspects.
Main Methods:
- Utilized the neurotoxin 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP) in mice.
- Administered MPTP to mice exhibiting IDPN-induced permanent dyskinesia.
- Assessed behavioral patterns and striatal dopamine (DA) levels post-MPTP administration.
Main Results:
- MPTP administration caused dramatic, biphasic effects on IDPN-induced behavioral patterns.
- IDPN did not alter striatal DA levels six weeks after syndrome onset compared to controls.
- IDPN appeared to reduce striatal levels of extraneuronal DA metabolites.
Conclusions:
- The nigrostriatal dopaminergic pathway may not be the primary driver for maintaining IDPN-related syndrome.
- Transient behavioral changes after MPTP could stem from acute effects on other dopaminergic areas or neurotransmitters.