Possible participation of NMDA and glycine receptors but not GABAA receptors in enflurane-induced opisthotonus in mice.
1. We previously reported that volatile anaesthetics produce incidences of a transient opisthotonus in mice, a sign of CNS stimulation. This study was performed to investigate mechanisms by which enflurane-induced opisthotonus (EIO) occurs. 2. The effects of pretreatment of N-methyl-D-aspartate (NMDA) antagonists dizocilpine (MK-801; DIZ) and ketamine (KET), GABAA antagonists picrotoxin (PIC), pentylenetetrazol (PTZ) and glycine antagonist strychnine (STR) on the incidence of EIO were determined. Prior to exposure to 2.0% enflurane in air, male ddN mice were given intraperitoneal injections of 0.2 mL saline (control), 0.5-5.0 mg/kg DIZ, 20-80 mg/kg KET, 2.9 mg/kg PIC, 40.0 mg/kg PTZ and 0.75 mg/kg STR. After the injection, the behavioural state of the mice was observed for 20 min (the pre-enflurane period). During the exposure to enflurane the time for immobilization, that is, anaesthetic induction time (IT), and the incidence of EIO were measured. 3. Dizocilpine (1.0-5.0 mg/kg) and KET (80 mg/kg) significantly (P < 0.01) reduced both the incidence of EIO and IT in a dose-dependent manner. During the pre-enflurane period DIZ produced incidences (5-40%) of transient seizures in a dose-dependent manner, while KET did not induce them at all. The two GABAA antagonists had no detectable effect on the EIO. Strychnine significantly enhanced the EIO. These CNS stimulants resulted in a 3-10% incidence of transient seizure and/or opisthotonus during the pre-enflurane period, but there was no correlation between DIZ-induced seizure and EIO. 4. These results suggest that the EIO is mediated by the NMDA and the STR-sensitive glycine receptors, but not the GABAA receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
Komatsu
H
H
Department of Anesthesiology and Emergency Medicine, Kagawa Medical School, Japan.
Nogaya
J
J
Ueki
M
M
Yokono
S
S
Ogli
K
K
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009128:Muscle Spasticity / Q000139:chemically induced*; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D018009:Receptors, Glycine / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology
D016291:Dizocilpine Maleate; D004737:Enflurane; D010433:Pentylenetetrazole; D010852:Picrotoxin; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D013331:Strychnine