Comparative Studies on Morphine- and Stress-Induced Analgesia and the Development of Tolerance to the Effects: Implication of Protein Synthesis Mechanism in the Process

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Abstract
Comparative studies were made in mice on morphine- and stress-induced analgesia (SIA) and on the development of tolerance to the effects. Cycloheximide (CYH), a potent protein synthesis inhibitor, did not affect the analgesic effect of morphine, but effectively suppressed the development of tolerance. CYH potentiated both foot shock (FS) and immobilized-water immersion (IW) SIA and inhibited the development of tolerance to FS-SIA. Incorporation of 3H-leucine into the TCA-insoluble fraction of mouse brain regions was inhibited by morphine, and the inhibition was reversed by the pretreatment with CYH. The inhibitory effect of morphine was lost in morphine tolerant animals. At the peak of SIA, incorporation of 3H-leucine was not changed in FS-SIA, but significantly inhibited in IW-SIA, and these effects were not modified by the pretreatment with CYH. The reduced incorporation of 3H-leucine in IW-SIA tolerant animals was partially reversed by CYH. The protein synthesis mechanism is greatly influenced by morphine or stresses, but the direct evidence for the implication of the mechanism in the process of producing analgesia and tolerance formation were not demonstrated. Differences in the underlying mechanisms were apparent between morphine and SIA and also between FS- and IW-SIA.