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.