[Differential effects of ketamine enantiomers on anesthetic levels and glutamate release in the hippocampus].
The anesthetic effects of ketamine enantiomers (40 and 100 mg.kg-1, i.p.) were evaluated in the rat by behavioral parameters such as the orienting response, the tail-pinch test and the spontaneous motor behavior including stereotyped behavior (circling and nodding). The intercellular glutamate concentration in the dorsal hippocampus was measured by brain microdialysis method. The analgesic and sedative effects of the S(+)-ketamine were more potent than those of the R(-)-ketamine at each dose. The incidence of stereotyped behaviors in R(-)-ketamine groups was higher than that of S(+)-ketamine groups. The basal release of glutamate under perfusion with normal artificial cerebrospinal fluid (ACSF) was unchanged after the administration of these enantiomers. Repeat perfusion with high-potassium ACSF (100 mM K+) for 20 min increased the glutamate content in vehicle-treated rats. This depolarization-related glutamate release was suppressed by ketamine, except in the 100 mg R(-)-ketamine group in which the stimulated glutamate release tended to increase after the treatment. The inhibitory effect on this stimulated glutamate release was marked in S(+)-ketamine groups. These results suggest that the anesthetic effects of ketamine enantiomers may be mediated at least in part, via regulation of depolarization-released glutamate release.
Murata
J
J
Department of Anesthesiology, Tokyo Women's Medical University, School of Medicine.
Ikeda
M
M
Takazawa
A
A
Kaneko
T
T
Suzuki
H
H
D000700:Analgesics / Q000494:pharmacology*; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005971:Glutamates / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D011188:Potassium / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects
D000700:Analgesics; D000778:Anesthetics, Dissociative; D005971:Glutamates; D007649:Ketamine; D011188:Potassium