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Effect of MK-801 on endogenous dopamine release in vivo
K Kashihara1, T Hamamura, K Okumura
1Department of Neuropsychiatry, Okayama University Medical School, Japan.
Abstract:
The effect of MK-801 on striatal dopamine (DA) release was investigated by using an in vivo microdialysis technique in the freely moving rat. Systemic injection of MK-801 (0.25, 0.5, 1, 2 mg/kg, i.p.) reduced the extracellular level of DA significantly and produced no change in the level of 3,4-dihydroxyphenylacetic acid. The behavioral observation, recorded simultaneously, revealed that MK-801, with smaller doses, produced ipsilateral circling toward the side with the dialysis probe. At larger doses, MK-801 predominantly evoked ataxia. These findings indicate that the behavioral effect of MK-801 may not be mediated via the release of DA.
Insights
MK-801 significantly reduced striatal dopamine release in rats but did not alter 3,4-dihydroxyphenylacetic acid levels. Behavioral changes observed suggest MK-801
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Dopamine (DA) plays a crucial role in motor control and reward pathways.
- MK-801 is an NMDA receptor antagonist with known behavioral effects.
Purpose of the Study:
- To investigate the impact of MK-801 on extracellular dopamine levels in the striatum.
- To correlate the neurochemical changes with observed behavioral alterations.
Main Methods:
- In vivo microdialysis technique in freely moving rats.
- Systemic administration of MK-801 at varying doses (0.25-2 mg/kg).
- Simultaneous behavioral observation and measurement of striatal DA and 3,4-dihydroxyphenylacetic acid.
Main Results:
- MK-801 administration dose-dependently reduced extracellular striatal DA levels.
- No significant changes were observed in 3,4-dihydroxyphenylacetic acid levels.
- Lower MK-801 doses induced ipsilateral circling, while higher doses caused ataxia.
Conclusions:
- The observed behavioral effects of MK-801, including circling and ataxia, may not be directly mediated by alterations in striatal dopamine release.
- MK-801's neurochemical actions on dopamine systems are distinct from its primary behavioral manifestations.