Tolerance to ketamine-induced blockade of cortical spreading depression transfers to MK-801 but not to AP5 in rats.
Tolerance to ketamine (KET) induced blockade of cortical spreading depression (CSD) was investigated in 31 rats anesthetized with pentobarbital. CSD was elicited by injection of 1 microl of 5% KCl into cortex at 15 min intervals and monitored by recording the accompanying slow potential waves. After control recording, five injections of KET (50 mg/kg) were applied at 75 min intervals. The first KET injection elicited CSD blockade lasting for 30-45 min at the near and for 60-75 min at the far electrode. The CSD blocking effect of subsequent injections gradually declined and was not recognizable after the fifth KET injection. MK-801 (2.5 mg/kg) injected to rats with fully developed KET tolerance 30 min after the last KET dose, failed to block CSD. Without KET pretreatment the same dosage of MK-801 induced CSD blockade lasting more than 1 h. KET tolerance did not prevent local CSD blockade in a cortical area superfused with 10(-3) mol/l AP5. It is concluded that repeated applications of KET may induce some conformational changes at binding site(s) in the N-methyl-D-aspartate (NMDA) controlled channels shared by both KET and MK-801.
Rashidy-Pour
A
A
Department of Physiology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
Motaghed-Larijani
Z
Z
Bures
J
J
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D013181:Cortical Spreading Depression / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate