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 administrationwere 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 ofmorphine and tramadolwas 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 ofmorphine 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.