Efectos de la combinación de melatonina con clorhidrato de ketamina sobre regímenes estándar de anestesia en ratas

Aim: Assess melatonin administration as an anaesthetic agent and establish whether combining this drug can decrease the required dosage of ketamine and/or enhance its effects. Materials and methods: Single and combined doses of melatonin (15 to 100 mg/kg) and ketamine (35, 50 and 70 mg/kg) are tested in 54 rats. Duration and depth of anaesthesia are assessed through recording righting and withdrawal reflexes. Four intervals of anaesthesia are defined (induction, general, surgical and full recovery). Results: Nine treatments are tested: (a) control and doses of 15 mg/kg melatonin and 35 mg/kg ketamine do not produce anaesthetic effects; (b) doses of 50 and 70 mg/kg ketamine and combination melatonin-ketamine 15 + 50 mg/kg effects of melatonin are verified. These effects are enhanced when combined with ketamine. Our results are compared with those obtained with combinations of ketamine and other anaesthetic drugs. The possible effect of the ketamine-melatonin combination on the GABAergic system and the NMDA receptors for glutamate is discussed. Conclusion: The melatonin-ketamine combination causes a rapid onset of anaesthesia and prolongs the effect of ketamine alone in rats. So, this study suggests that melatonin modulates mechanisms involved in the induction of anaesthesia by ketamine.