The present study has been designed to pharmacologically investigate the role of opioid and gamma-aminobutyric acid receptors on the seizurogenic effect of tramadol. A single injection of pentylenetetrazole (80 mg/kg) was used to elicit seizure activity in mice. Seizures were assessed in terms of the time latency of the onset of Straub's tail phenomenon, onset of jerky movements of whole body, convulsions and death. Tramadol administration (50 mg/kg) caused a marked increase in seizurogenic activity of pentylenetetrazole as measured in terms of a significant decrease in the time latency of the onset of Straub's tail phenomenon, jerky movements of whole body, convulsions and death. Moreover, prior administration of naloxone (2 mg/kg) and gabapentin (25 mg/kg), respectively, attenuated the seizurogenic activity that tramadol exerted on pentylenetetrazole-treated mice. Furthermore, prior administration of naloxone (2 mg/kg) and gabapentin (25 mg/kg), respectively, also attenuated the seizurogenic activity exerted by tramadol per se. Therefore, it is suggested that tramadol exerts a seizurogenic effect on mice possibly via an opioid-dependent gamma-aminobutyric acid inhibitory pathway.