Time-dependent effects of in vivo pertussis toxin on morphine analgesia and G-proteins in mice.
Previous studies have indicated a long-duration of effect of in vivo pertussis toxin (PTX) on morphine analgesia in the mouse. However, the time-course of potency changes in morphine analgesia as determined in dose-response studies and biochemical correlates of PTX treatment have not been reported to date. Therefore, in the present studies the effects of in vivo PTX on morphine analgesia ED50 and PTX-catalyzed incorporation of [32P]-ADP-ribose and synapsin content in mouse spinal cord were examined. Mice were injected IT & ICV with saline or PTX (total dose = 0.2 microg) and tested for systemic morphine analgesia (tail-flick) 1, 10, 16 & 40 days later. There was no significant decrease in morphine potency 1 day following PTX treatment, whereas PTX produced a significant decrease in morphine potency at 10, 16 & 40 days. Concurrent decreases in the incorporation of [32P]-ADP-ribose in spinal cord by PTX were observed on days 10, 16 & 40. No changes were observed in synapsin content which suggests that the effect was not nonspecific. This study indicates that in vivo PTX produces co-ordinate long-lasting effects in both functional (analgesia) and biochemical (Gi/o-proteins) assays.