Abstract
Opioids exert different effects on seizure threshold
based on their doses and the models. P-glycoprotein (p-gp) prevents various
substances from entering the brain. Morphine is a p-gp substrate. The aim of
this study was to investigate the effects of morphine on strychnine-induced
convulsion in ovariectomized mice and to see whether verapamil as a p-gp pump
inhibitor interferes with that effects Methods:
Female mice were ovariectomized to
remove the gonadal
sex hormones Thirty minutes prior to induction of
convulsion by subcutaneous injection of strychnine, the animals were received
morphine (1, 2, 3mg/kg), naloxone (1, 2, 5mg/kg), verapamil (20mg/kg) and
morphine (3mg/kg)+verapamil (20mg/kg) intraperitoneally. Then, the onset of
convulsion and time to death were recorded. The significance of differences for
the seizure parameters were assessed using one-way analysis of variance (ANOVA)
followed by least significant difference (LSD) post hoc comparison or unpaired
t-test. Results: The results showed that morphine produced
anticonvulsant effect by prolonging the
time to death (P < 0.001) and naloxone had no effect on strychnine-induced
convulsion. Verapamil alone had no effect on the convulsion whereas, it
significantly (p < 0.05) reduced the anticonvulsant effect of morphine by
reducing the time to death. Conclusion: Anticonvulsant activity
of morphine is mediated through different mechanisms. The reduced anticonvulsant
effect of morphine by verapamil seems to be because of increase in morphine
concentration in brain.