抄録
The anesthetic drug ketamine (KT) has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, the intraperitoneal KT-induced alterations in several behaviors and the toxic interactions with the popular co-abused psychostimulants cocaine (COC) and methamphetamine (MA) were examined in male ICR mice. Methods and Results: A single dose of KT caused hyperlocomotion in a low (30 mg/kg) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg) dose group. However, no behavioral alterations derived from enhanced stress-related depression nor anxiety were observed in the forced swimming or the elevated plus-maze test. For the non-fatal dose COC (30 mg/kg) or MA (4 mg/kg) group of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced stress-related and anxiety-related behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg)- or MA (15 mg/kg)-KT group, KT attenuated the severity of seizures dose-dependently, but the mortality rate was significantly increased by the high dose KT. Discussion and Conclusion: These results demonstrated an absence of certain painful behavioral alterations (e.g. anxiety) following a single KT treatment, which may promote an overdose. Furthermore, in spite of the KT-induced anticonvulsant effects, the lethal effects of COC and MA were enhanced by KT.
