title: Tolerance to ketamine-induced blockade of cortical spreading depression transfers to MK-801 but not to AP5 in rats.
abstract: 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.
authors.affiliation: Department of Physiology, School of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Rashidy-Pour
authors.forename: Z
authors.initials: Z
authors.lastname: Motaghed-Larijani
authors.forename: J
authors.initials: J
authors.lastname: Bures
mesh_terms: 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
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate