The role of alpha-2 adrenoceptors in the anticonvulsant effects of adenosine on pentylenetetrazole-induced seizure threshold in mice

• CHA exerted anti-seizure effect, while 8-CPT did not change the seizure threshold.
• Combination of yohimbine and CHA increased seizure latency showing additive effect.
• The additive effect of yohimbine and CHA was inhibited by 8-CPT or clonidine.
• Clonidine inhibited the anticonvulsant effects of CHA.
• Combination of low dose of 8-CPT and clonidine inhibited anti-seizure effect of CHA.

Adenosine has anticonvulsant effects in various models of seizures. Alpha-2 adrenoceptors have also demonstrated different effects in different models of epilepsy. In this study, the role of alpha-2 adrenoceptors in the anticonvulsant effects of adenosine in mice was determined according to the method of intravenous pentylenetetrazole-induced seizure. In this study, N6-cyclohexyladenosine (CHA) (a selective A1 receptor agonist), clonidine (an alpha-2 adrenoceptors agonist), yohimbine (an alpha-2 adrenoceptors antagonist) and 8-cyclopentyl-1,3-dimethylxanthine (8-CPT) (a selective A1 receptor antagonist) were used. CHA at doses of 0.5, 1 and 2 mg/kg significantly increased seizure threshold with the maximum anticonvulsant effect at 2 mg/kg. Yohimbine (0.1, 1 and 10 mg/kg), clonidine (0.1, 0.5, 1 and 2 mg/kg) and 8-CPT (0.5, 1, 2 and 4 mg/kg) had no effect on seizure by itself. Combination of yohimbine (10 mg/kg) and CHA (0.25 mg/kg) increased clonic seizure latency showing that yohimbine and CHA have an additive effect. Increasing the seizure threshold created by combining ineffective doses of yohimbine (10 mg/kg) and CHA (0.25 mg/kg) was completely inhibited by 8-CPT (4 mg/kg) or clonidine (1 and 2 mg/kg). Clonidine (0.5, 1 and 2 mg/kg) inhibited the anticonvulsant effects of CHA (2 mg/kg). Combination of 8-CPT (1 mg/kg) and clonidine (0.5 mg/kg) which completely inhibited the anticonvulsant effect of CHA (2 mg/kg) indicates that 8-CPT and clonidine have an additive effect. In conclusion, adenosine and yohimbine exhibit an additive effect on the enhancement of the pentylenetetrazole-induced seizure threshold in mice, indicating the interaction of alpha-2 adrenoceptors and A1 adenosine receptors.