The interaction between morphine and propranolol in chemical and electrical seizure models of mice.

Abstract

OBJECTIVES: Morphine and propranolol have different effects on seizure. Several studies have shown interaction between adrenergic and opioid systems in different models. In this study, interaction between morphine and propranolol in different seizure models was examined in mice. METHODS: In this study, three seizure models, including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ and electroshock, were examined in mice. Animals were injected with different doses of morphine or propranolol in the 60th and 45th min, before seizure induction, respectively. RESULTS: Acute administration of propranolol or lower doses of morphine induced an anticonvulsant effect in intravenous PTZ, intraperitoneal PTZ and electroshock-induced seizure models; on the contrary, higher doses of morphine exert proconvulsant effects in all three models. Also additive anticonvulsant effect of propranolol and lower doses of morphine was observed in all examined models. The additive anti-seizure effect of propranolol and lower doses of morphine was blocked by naltrexone in intraperitoneal PTZ model. Moreover, the anticonvulsant effect of propranolol was inhibited by naltrexone in intraperitoneal PTZ seizure model of mice. Propranolol restrained the proconvulsant effects in higher doses of morphine in clonic seizures of intravenous and intraperitoneal PTZ models. DISCUSSION: In conclusion, we believe that this is the first study that has indicated the interaction of propranolol and lower doses of morphine in the anticonvulsant effects in three seizure models of intravenous PTZ, intraperitoneal PTZ and electroshock. The involvement of μ-opioid receptor in this interaction was also demonstrated. Simultaneously, we showed the interaction between propranolol and higher doses of morphine in proconvulsant effects.