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Life Sci. 1989;44(21):1593-9.

In vivo demonstration of the enhancement of MK-801 by L-glutamate.

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Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477.


MK-801 infused bilaterally into the nucleus accumbens of rats produced a dose-related increase in locomotor activity that was not blocked by intra-accumbens infusion of haloperidol (2.5 micrograms). Intra-accumbens infusion of L-glutamate (1.0 microgram) was without effect when administered alone, but significantly enhanced the increase in locomotor activity produced by MK-801 (5.0 micrograms). The inactive isomer of MK-801 did not produce hypermotility and L-glutamate did not enhance amphetamine(intra-accumbens)-induced hypermotility. These results extend to an in vivo model electrophysiological and radioligand binding studies demonstrating an enhancement of MK-801 activity by L-glutamate. The results also reinforce the concept that such an enhancement would occur during an escalation of excitatory amino acid levels accompanying pathological overload and, thus, would trigger a compensatory neuronal protection by MK-801.

[Indexed for MEDLINE]

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