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Cognitive changes in mice following moderate MPTP exposure
H Tanila1, M Björklund, P Riekkinen
1Department of Neuroscience and Neurology, University of Kuopio, Finland. Heikki.Tanila@uku.fi
Abstract:
We evaluated the cognitive effects of two moderate doses (30 mg/kg x 3 every 12 h and 20 mg/kg x 6 every 8 h, i.p.) of 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in mice. The dose of 30 mg/kg x 3 caused about 60% depletion of striatal dopamine but did not reduce the levels of its metabolites. Mice treated with MPTP did not differ from controls in their motor behavior in the open field. Mice treated with MPTP were comparable to controls in T-maze delayed alternation with fixed delays but were impaired when trials with mixed 20 s and 120 s delays were presented, indicative of a spatial working memory impairment. Dexmedetomidine at 10 microg/kg (s.c.) slightly improved delayed alternation performance in all groups but also slowed initiation of the motor response. Mice treated with MPTP at the dose of 30 mg/kg x 3 were less sensitive to this adverse effect of dexmedetomidine. The impairment in spatial working memory after MPTP exposure in mice parallels the findings in monkeys, but the deficit is much less severe.
Insights
1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in mice caused spatial working memory deficits, similar to monkeys but less severe. MPTP-treated mice showed reduced sensitivity to dexmedetomidine
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin used to model Parkinson's disease.
- Cognitive deficits, particularly in working memory, are a feature of Parkinson's disease.
Purpose of the Study:
- To evaluate the cognitive effects of MPTP administration in mice.
- To assess the impact of MPTP on spatial working memory and motor behavior.
- To investigate the interaction between MPTP and dexmedetomidine.
Main Methods:
- Mice were administered two different moderate doses of MPTP.
- Cognitive function was assessed using the T-maze delayed alternation task.
- Motor behavior was evaluated in the open field test.
- The effects of dexmedetomidine on cognitive and motor performance were examined.
Main Results:
- MPTP treatment (30 mg/kg x 3) significantly depleted striatal dopamine levels.
- MPTP-induced mice exhibited impaired spatial working memory at longer delays.
- No significant motor deficits were observed in the open field test.
- Dexmedetomidine improved delayed alternation but slowed motor response initiation; MPTP-treated mice were less sensitive to this effect.
Conclusions:
- MPTP induces spatial working memory deficits in mice, mirroring findings in non-human primates.
- The observed cognitive impairment is less severe than in monkeys.
- MPTP exposure may alter sensitivity to sedative-hypnotic agents like dexmedetomidine.
