Introduction: In the Kindling as a model, low and repeated electrical or chemical stimulation, can elevate the neural network excitability and raise the epileptiforms seizure. Regarding the wide distribution of opioid receptors in different brain areas from one hand, and the paradoxical effects of morphine on elevation and/or alleviation of the pain sensation and excitability, at different doses on the other hand, present study is designed to search the effect of ultra low dose of morphine on seizure induced by Pentylentetrazol (PTZ). Methods: PTZ (32 mg/kg i.p.) was used at 12 constitutive days to kindle the male Wistar rats (200-250 gr). Animals were treated by saline & morphine (0.1 µg/kg, 1 g/kg, 10 g/kg and 10 mg/kg), 30 min before PTZ administration respectively and and seizure severity was recorded during the 30 min after PTZ treatments. Results: Morphine at the dose of 10 mg/kg elevated the seizure….and accelerated the Morphine at dose of 10 mg/kg was able to elevate the seizure intensity and accelerate the kindling process (p<0.001). In comparison, morphine at dose of 10 µg/kg, attenuated the seizure intensity and kindling development (p<0.05) Conclusion: We showed a paradoxical effect of morphine on seizure induced by PTZ. For explanation, it can be mentioned that, morphine at ultra low dose, can elicit the stimulatory signaling pathway of Gs protein, rater than the inhibitory one (Gi). It seems that the activity of Gs signaling can lead to the attenuation of PTZ induced seizure. In contrast, activation of Gi signaling using ordinary doses of morphine can lead to potentate the PTZ induced seizure.

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