Stimulatory and inhibitory effects of morphine on pentylenetetrazol-induced epileptic activity in rat

Abstract

Aims The present study attempts to evaluate the effects of different doses of morphine on experimental epileptiform activity caused by pentylenetetrazol (PTZ) in rats. Methods Thirty adult male rats were assigned to saline (n = 5), morphine (2, 5, and 10 mg/kg, n = 15), naloxone (1 mg/kg, n = 5), and pre-treated with naloxone+morphine (1 + 10 mg/kg, n = 5) groups. The animals were anesthetized with ketamine + xylazine (80 + 8 mg/kg), and then a bipolar electrode was implanted into the CA1 (AP: −2.76 mm, ML: −1.4 mm and DV: 3 mm). To evaluate the effects of drugs on spike count and their amplitudes by elab amplifier, after drug administration for 25 min, PTZ (80 mg/kg, i.p.) was injected to induce epileptiform activity. Finally, diazepam (10 mg/kg) was used to suppress epileptic activity. Results The results revealed that morphine at a dose of 2 mg/kg decreased, and at doses of 5 and 10 mg/kg had an increasing effect on seizure-like events (SLEs). Nevertheless, morphine at a dose of 10 mg/kg enhanced SLEs significantly (p < 0.01). Naloxone at a dose of 1 mg/kg had no significant effect on the spike count but increased amplitude of them (p < 0.001). Moreover, being pretreatment with naloxone at a dose of 1 mg/kg, the morphine group showed significantly increased in the spike count (p < 0.05). Conclusions Morphine has biphasic effects on PTZ-induced epileptiform activities that way at a low dose has an inhibitory effect, but if the dose is increased, it will intensify the desired event and that the stimulatory effects of morphine appear not to be via opioid receptors.