The effect of gabapentin on the withdrawal signs in morphine-dependent male rats



Acute morphine withdrawal is considered to be the physical manifestation of dependence, emerging when morphine administration is stopped or after the administration of an opiate antagonist, such as naloxone. Gabapentin, which is an antiepileptic, agent, enhances the analgesic effect of morphine in healthy volunteers, but its effect on morphine dependence and withdrawal signs has not determined yet. This study was performed to evaluate the effects of gabapentin on withdrawal signs in morphine dependent male rats. Four groups of male rats (n=32) weighing 220-250g tested for withdrawal signs: control, morphine, gabapentin and gabapentin-morphine treated. Rats received morphine (10 mg/kg, s.c.), gabapentin or both of them twice a day for 9 days. Control rats received normal saline. On the 9th day, two hours after the last dose of morphine the rats were challenged for withdrawal by administration of naloxone (2.5 mg/kg, i.p.) and observed for various withdrawal signs such as diarrhea, jumping, writhing, and fore paw tremor over a period of 20 minutes. All of the withdrawal signs were observed in morphine dependent rats after naloxone administration. In gabapentin-morphine treated rats, writhing and diarrhea were significantly increased while jumping, fore paw tremor and weight loss were attenuated as compared to saline treated rats. The results of this study showed that co-administration of gabapentin attenuated some withdrawal signs such as jumping, fore paw tremor and weight loss in morphine dependent rats, while diarrhea and writhing significantly increased.