In vivo demonstration of the enhancement of MK-801 by L-glutamate.
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.
Raffa
R B
RB
Department of Biological Research, Janssen Research Foundation, Spring House, PA 19477.
Ortegón
M E
ME
Robisch
D M
DM
Martin
G E
GE
D000818:Animals; D003986:Dibenzocycloheptenes / Q000008:administration & dosage / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000494:pharmacology*; D018698:Glutamic Acid; D006220:Haloperidol / Q000494:pharmacology; D007700:Kinetics; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains
D003986:Dibenzocycloheptenes; D005971:Glutamates; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D006220:Haloperidol