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Opioid mechanisms of some behavioral effects of ketamine
1Department of Pharmacodynamics, Medical Academy, Lublin, Poland.
Abstract:
The effect of naloxone on the duration of sleep and on analgesia produced by ketamine, and on the development of tolerance and cross-tolerance with morphine to ketamine analgesic effects were investigated in mice. Ketamine produced a dose-dependent analgesia. Naloxone (4 mg/kg) significantly inhibited the analgesic effects of ketamine (40 mg/kg), but (given in a dose of 2 mg/kg) did not affect the duration of ketamine sleep. Chronic administration of ketamine (160 mg/kg twice daily for 7 days) resulted in a gradual shortening of ketamine sleep and in the development of tolerance to the analgesic action of ketamine. There also developed cross-tolerance between analgesic effects of morphine and ketamine. Ketamine (20 mg/kg) significantly inhibited symptoms of morphine abstinence produced in morphine-pelleted mice by naloxone administration or by pellet removal. The results suggest that at least some elements of the mechanism of action of ketamine and morphine may be common and related to the endogenous opioid system.
Insights
Naloxone (an opioid antagonist) inhibited ketamine
Area of Science:
- Pharmacology
- Neuroscience
Background:
- Ketamine exhibits analgesic properties.
- The endogenous opioid system's role in ketamine's effects is not fully understood.
Purpose of the Study:
- To investigate the interaction between naloxone and ketamine.
- To examine the development of tolerance and cross-tolerance to ketamine's analgesic effects with morphine.
Main Methods:
- Mice were administered ketamine and naloxone.
- Analgesia and sleep duration were measured.
- Chronic ketamine administration and morphine abstinence models were used.
Main Results:
- Naloxone inhibited ketamine-induced analgesia but not sleep duration.
- Chronic ketamine led to tolerance and cross-tolerance with morphine.
- Ketamine mitigated morphine abstinence symptoms.
Conclusions:
- Ketamine and morphine share common mechanisms potentially involving the endogenous opioid system.
- Naloxone's antagonism suggests opioid receptor involvement in ketamine analgesia.