Evaluation the effect of co-administration of gabapentin and sodium selenite on the development of tolerance to morphine analgesia and dependence in mice

The fundamental mechanisms including development of tolerance and dependence on opioides are relationship between glutamatergic system and analgesic effect of opioides. However other reports show only the analgesic effect of gabapentin on glutamatergic system and NMDA receptors. In this study we evaluate individual effects of gabapentin and sodium selenite alone as well as co-administration of these drugs on the development and dependence to morphine. Experiments were performed on 18 groups (n=8) of albino swiss male mice weighing 25-30 g. Animals received saline (10 ml/kg, i.p.), vehicle of drugs (saline normal- 10 ml/kg, i.p.) with morphine (50 mg/kg, i.p.), morphine with gabapentin (10, 20, 40 mg/kg, i.p.) or sodium selenite (1, 2, 4 mg/kg, i.p.), morphine with both of drugs (gabapentin 10 mg and sodium selenite 1 mg) for a period of four days. On the fifth day, a hot-plate test was done after administration of test dose of morphine (9 mg/kg, i.p.). In order to assay the effect of gabapentin and sodium selenite on morphine dependence, animals received morphine (50 mg/kg, s.c.) and saline or drugs for five days. Two hours after the last dose of morphine, the naloxone (4 mg/kg, i.p.) was injected and withdrawal signs (jumping and standing on feet) were recorded for 30 minutes. The results showed that gabapentin (in all three doses) and sodium selenite (in two higher doses) decreased morphine tolerance (p<0.05- 0.001) and co-administration of these drugs had the additive effect (p<0.05). In dependence studies, the administration of gabapentin and sodium selenite alone decreased withdrawal signs (in two higher doses- jumping: p<0.01-0.001, standing on feet: p<0.05-0.01) and gabapentin pluse sodium selenite had additive effect only on jumping (p<0.001). Our data indicate that glutamatergic system and additive effect of the related antagonists have an essential role on development of tolerance and dependence to morphine.