Interaction between ketamine and ethanol in rats and mice.
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.
Fidecka
S
S
Department of Pharmacodynamics, Medical Academy, Lublin, Poland.
Langwiński
R
R
D000818:Animals; D004347:Drug Interactions; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology* / Q000633:toxicity; D007649:Ketamine / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D000431:Ethanol; D007649:Ketamine