Fidecka S, Langwiński R
Department of Pharmacodynamics, Medical Academy, Lublin, Poland.
Pol J Pharmacol Pharm. 1989 Jan-Feb;41(1):23-32.
The development of tolerance to analgesic effects of ethanol and ketamine, development of cross-tolerance between those drugs, and the effects of ketamine on the symptoms of ethanol abstinence were investigated in mice and rats. The analgesic action of ethanol (2.8 g/kg in rats, 5 g/kg in mice) was significantly reduced in the animals chronically treated with ethanol. Chronic treatment with ketamine (100 mg/kg in rats, 160 mg/kg in mice twice daily for 7 days) resulted in development of tolerance to the analgesic effects of ketamine. Cross-tolerance developed to the analgesic action of ketamine in mice and rats receiving ethanol chronically. A chronic treatment with ketamine resulted in development of significant cross-tolerance to the antinociceptive action of ethanol. Ketamine significantly attenuated the symptoms of ethanol abstinence (head shakes) in mice (20 mg/kg) and rats (25 mg/kg). Naloxone pretreatment (2 mg/kg) antagonized the inhibitory action of ketamine on the ethanol abstinence in rats. Doses of 12.5-75 mg/kg of ketamine abolished or significantly inhibited the ethanol abstinence symptoms (audiogenic seizures) in rats. The results demonstrate some similarities of the action of ketamine and ethanol and suggest a possibility that the endogenous opioid system participates in the mechanisms of action of the investigated compounds.
在小鼠和大鼠中研究了对乙醇和氯胺酮镇痛作用的耐受性发展、这些药物之间交叉耐受性的发展以及氯胺酮对乙醇戒断症状的影响。长期用乙醇处理的动物中，乙醇（大鼠2.8 g/kg，小鼠5 g/kg）的镇痛作用显著降低。长期用氯胺酮（大鼠100 mg/kg，小鼠160 mg/kg，每日2次，共7天）处理导致对氯胺酮镇痛作用产生耐受性。长期接受乙醇的小鼠和大鼠对氯胺酮的镇痛作用产生交叉耐受性。长期用氯胺酮处理导致对乙醇的抗伤害感受作用产生显著交叉耐受性。氯胺酮显著减轻了小鼠（20 mg/kg）和大鼠（25 mg/kg）的乙醇戒断症状（头部抖动）。纳洛酮预处理（2 mg/kg）拮抗了氯胺酮对大鼠乙醇戒断的抑制作用。12.5 - 75 mg/kg剂量的氯胺酮消除或显著抑制了大鼠的乙醇戒断症状（听源性惊厥）。结果表明氯胺酮和乙醇的作用有一些相似之处，并提示内源性阿片系统可能参与了所研究化合物的作用机制。
