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首页> 外文期刊>BMC Neuroscience >Behavioral effects of ketamine and toxic interactions with psychostimulants
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Behavioral effects of ketamine and toxic interactions with psychostimulants

机译：氯胺酮的行为影响以及与精神刺激药的毒性相互作用

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Background 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, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p.) KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC) and methamphetamine (MA), were examined in ICR mice. Results A single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p.) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p.) dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p.) or MA (4 mg/kg, i.p.) caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms) in the elevated plus-maze test. For the COC (30 mg/kg) or MA (4 mg/kg) groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.)- or MA (15 mg/kg, i.p.)-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT. Conclusion Our results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single dose of KT treatment, and in spite of the KT-induced anticonvulsant effects and attenuation of stress- and anxiety-related behaviors caused by COC or MA, the lethal effects of these psychostimulants were increased by KT.
机译：背景技术据报道，麻醉药氯胺酮（KT）是滥用药物，多药使用者中已观察到致命病例。在本研究中，考虑到其他药物可能会增强KT的毒性作用，并导致KT诱导过量服用，而没有使受试者意识到由于减轻几种痛苦的主观症状而引起的危险，腹膜内（ip）KT在ICR小鼠中检查了与流行的共同滥用药物，精神刺激剂可卡因（COC）和甲基苯丙胺（MA）引起的行为改变和毒性相互作用。结果单剂KT在低剂量组（30 mg / kg，i.p.）引起运动过度，而低剂量运动后在高剂量组（100 mg / kg，i.p.）引起运动过度。但是，在强迫游泳或高迷迷宫测试中，未观察到因压力相关性抑郁或焦虑加剧而引起的行为改变。一次非致命剂量的COC（30 mg / kg，ip）或MA（4 mg / kg，ip）会引起运动过度，强迫游泳试验中游泳行为中与压力相关的抑郁情绪以及与焦虑相关的行为变化（偏好（对于闭合的手臂）在高迷宫测试中。对于同时使用KT共同治疗的COC（30 mg / kg）或MA（4 mg / kg）组的小鼠，高剂量KT抑制了精神兴奋药诱发的运动过度，并且上述情况下精神兴奋药诱发的行为改变低剂量和高剂量的KT均使试验相反。对于仅毒性剂量的COC（70 mg / kg，腹腔）或MA（15 mg / kg，腹腔）组，在某些动物中观察到了死亡率和严重的癫痫发作。在有毒剂量的精神兴奋剂-KT组中，KT剂量依赖性地减轻了癫痫发作的严重程度。但是，与高剂量KT联合治疗可大大提高死亡率。结论我们的结果表明，尽管在单剂KT治疗后不存在与压力相关的抑郁和焦虑相关行为改变，并且尽管存在KT诱导的抗惊厥作用以及与压力和焦虑相关的行为减弱由COC或MA引起的这些精神刺激药的致死作用因KT而增加。

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