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Behavioural effects and supersensitivity in the rat following intranigral MPTP and MPP+ administration
1Laboratory of Psychobiology, University of Düsseldorf, F.R.G.
Abstract:
Unilateral intranigral injections of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (1-methyl-4-phenylpyridine) were given to young rats and unilateral intranigral injections of MPTP were given to old rats. MPTP in old rats and MPP+ in young rats induced ipsiversive circling for at least one week after injection and contraversive circling after the systemic administration of apomorphine; the number of D-2 receptors (Bmax) in the striatum of the injected hemisphere increased compared with that of control rats. MPTP in young rats induced only short-lasting ipsiversive circling and no contraversive circling after apomorphine; the number of striatal D-2 receptors did not increase. These results suggest that the neurotoxicity of MPTP is age-dependent in the rat, and that MPTP has neurotoxic effects on the nigrostriatal dopaminergic system in old rats and induces dopamine receptor supersensitivity in the denervated striatum.
Insights
The neurotoxicity of MPTP is age-dependent in rats. Old rats exhibit significant nigrostriatal dopaminergic system damage and dopamine receptor changes, unlike young rats.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- The nigrostriatal dopaminergic system is crucial for motor control.
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a neurotoxin used to model Parkinson's disease.
- Age can influence the susceptibility to neurotoxins.
Purpose of the Study:
- To investigate the age-dependent neurotoxicity of MPTP and its metabolite MPP+ (1-methyl-4-phenylpyridine) in rats.
- To examine the effects on the nigrostriatal dopaminergic system and dopamine D-2 receptors.
Main Methods:
- Unilateral intranigral injections of MPTP or MPP+ were administered to young and old rats.
- Behavioral assessments (circling) were performed after drug administration.
- Dopamine D-2 receptor density (Bmax) in the striatum was quantified.
Main Results:
- MPTP in old rats and MPP+ in young rats induced persistent ipsiversive circling and apomorphine-induced contraversive circling.
- These treatments also led to an increase in striatal D-2 receptor density (Bmax).
- MPTP in young rats caused only transient circling and no significant change in D-2 receptors.
Conclusions:
- MPTP neurotoxicity is age-dependent in the rat model.
- Old rats are more vulnerable to MPTP's effects on the nigrostriatal dopaminergic system.
- MPTP induces dopamine receptor supersensitivity in the denervated striatum of older rats.