Effect of Oseltamivir on hyperalgesia induced by low concentrations of morphine and morphine tolerance in Drosophila melanogaster

Morphine has been known as a drug with different paradoxical effects، analgesic and hyperalgesic. On the other hand، repeated morphine administration، induces morphine tolerance in mammals. The aim of recent study is investigating tolerance to morphine in Drosophila melanogaster and the effect of Oseltamivir (an inhibitor of G2 receptors) on hyperalgesia induced by low concentrations of morphine and morphine tolerance. In this study، stage 3 of larvae and adult state of wild Drosophila melanogaster were used. For evaluating the effect of Oseltamivir on hyperalgesic effect of low concentration Morphine، Oseltamivir (0. 2 mg/l) and low concentrations of morphine were added to media culture. Then behavior of larvae and adults to thermal (using Hot plate، 47˚C) and chemical (capsaicin and acetic acid) pain stimulations were recorded. For morphine tolerance experiments in larvae، repeated morphine administration (0. 1 and 0. 01 mg/l) was done and their response to thermal pain was evaluated. The same method was used in adults but with other doses of morphine (200 and 300 mg/l). Finally to investigate the mechanism of morphine tolerance، Oseltamivir was administered too. morphine tolerance was occurred in Drosophila melanogaster similar to mammals. Repeated morphine administration diminished anti nociceptive effects of morphine (p<0. 001). Oseltamivir reduced morphine tolerance and hyperalgesic effects of low concentration morphine in both pain models (thermal and chemical nociception)، (p<0. 01). opioid systems can involve pain modulation (hyperalgesia and analgesia) in Drosophila like vertebrates. Our results showed inhibition of excitatory G-protein (Gs) by Oseltamivir، inhibit morphine induced hyperalgesia and this is another confirmation for involvement of excitatory G-proteins in morphine induced tolerance.