Proconvulsant effects of tramadol and morphine on pentylenetetrazol-induced seizures in adult rats using different routes of administration.

Tramadol is frequently used as a pain reliever. However, it has been sometimes noted to have the potential to cause seizures. Because of its dual mechanism of action (both opioid and nonopioid), the adverse effect profile of tramadol can be different in comparison with single-mechanism opioid analgesics, such as morphine. In the present study, the facilitatory effects of tramadol and morphine on pentylenetetrazol-induced seizures using different routes of administration were compared in rats. Adult female rats were divided into six groups and continuously received saline, morphine, or tramadol on a daily basis for 15 days [gavage (PO) or intraperitoneal (IP)]. An increasing dose of morphine and tramadol was used to prevent resistance to repetitive dose (20-125 mg/kg). Following one week of withdrawal period and 30 min before the seizure induction (PTZ=80 mg/kg, IP), each group of rats was further divided into subgroups that received saline, morphine, or tramadol for the second time on the 22nd day of the experiment. Results showed that, while morphine, tramadol, and their administration had different effects on seizure behaviors, both acute and chronic administrations of morphine and tramadol potentiated PTZ-induced seizures. However, there was no significant difference between morphine and tramadol in terms of seizure severity. Effects of morphine and tramadol on PTZ-induced seizures were also stable following one week of withdrawal. In conclusion, this study indicated similar severity in the proconvulsant effect of morphine and tramadol on PTZ-induced seizures, which might depend on their similar effects on GABAergic pathways.