Effect of ultra low dose morphine on seizure induced by pentylentetrazol

Introduction: In the Kindling-induced seizure model, low and repeated electrical or chemical stimulations, can elevate the neural network excitability and induce epileptiform seizures. Opioid receptors are widely distributed in different areas of the brain. On the other hand, morphine has paradoxical effects and induces elevation or alleviation of the pain sensation and excitability, at different doses. The present study is designed to investigate the effect of ultra low dose morphine on seizures induced by pentylentetrazol (PTZ). Methods: PTZ (32 mg/kg i.p.) was administered for 12 constitutive days to kindle the male Wistar rats (200-250 g). Animals were treated by saline or morphine (0.1 μg/kg, 1 μ g/kg, 10 μ g/kg and 10 mg/kg), 30 min before PTZ administration (n = 7-9) and seizure severity was recorded during 30 min after PTZ administrations. Results: Morphine at the dose of 10 mg/kg was able to elevate the seizure intensity and accelerate the kindling process (p<0.001), but at the dose of 10 μg/kg, attenuated the seizure intensity and kindling development (p<0.05). Conclusion: The reason for this paradoxical effect of morphine on PTZ-induced seizure could be that morphine, at ultra low doses, can elicit the stimulatory signaling pathway of Gs protein, rather than the inhibitory Gi pathway. It seems that ultra low does of morphine by inducing the activity of Gs signaling can lead to the attenuation of PTZinduced seizures, while activation of Gi signaling using ordinary doses of morphine can cause potentiation of PTZinduced seizures.