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MK-801 fails to modify the effect of methamphetamine on dopamine release in the rat striatum
K Kashihara1, K Okumura, M Onishi
1Department of Neuropsychiatry, Okayama University Medical School, Japan.
Abstract:
The effect of MK-801 at a dose of 0.5 mg kg-1, i.p., on methamphetamine-induced (MAP; 4 mg kg-1, i.p.) dopamine (DA) release was examined in the striatum of freely moving rats using an in-vivo microdialysis method. Combined treatment of MK-801 with MAP did not modify the MAP-induced increase in extracellular DA levels or the decrease in 3,4-dihydroxyphenylacetic acid levels. These findings suggest that MK-801 fails to modify the acute effect of MAP on DA release in the striatum. The blocking effect of MK-801 on the development of MAP-induced behavioral sensitization is unlikely to be mediated by DA neurons.
Insights
MK-801 did not alter methamphetamine
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Methamphetamine (MAP) causes significant dopamine (DA) release in the striatum.
- MK-801 is an NMDA receptor antagonist with potential modulatory effects on neurotransmitter systems.
Purpose of the Study:
- To investigate the impact of MK-801 on methamphetamine-induced dopamine release in rat striatum.
- To determine if MK-801 influences the acute dopaminergic effects of methamphetamine.
Main Methods:
- In-vivo microdialysis in freely moving rats.
- Administration of MK-801 (0.5 mg/kg) and methamphetamine (4 mg/kg).
- Measurement of extracellular dopamine and 3,4-dihydroxyphenylacetic acid levels.
Main Results:
- Combined MK-801 and methamphetamine treatment did not alter the increase in extracellular DA induced by methamphetamine.
- MK-801 did not affect the decrease in 3,4-dihydroxyphenylacetic acid levels caused by methamphetamine.
- No significant modification of acute methamphetamine's effects on striatal dopamine release was observed.
Conclusions:
- MK-801 does not acutely affect methamphetamine-induced dopamine release in the rat striatum.
- The mechanism by which MK-801 blocks behavioral sensitization to methamphetamine is likely independent of direct modulation of dopamine neurons.