Effect of Curcumin Against Pentylenetetrazol-Induced Seizure Threshold in Mice: Possible Involvement of Adenosine A1 Receptors

Curcumin, obtained from Curcuma longa, has been in use for manifold human disorders. The present study explores the effect of curcumin against pentylenetetrazol (PTZ) seizure threshold in mice. The possible involvement of adenosine receptor(s) mechanism was also investigated. Minimal dose of PTZ (i.v., mg/kg) needed to induce different phases of convulsions were recorded as an index of seizure threshold. Curcumin (20-120 mg/kg, p.o.) produced an increase in seizure threshold for convulsions induced by PTZ i.v. infusion. The anticonvulsant effect of curcumin (80 mg/kg) was prevented by 8-phenyltheophylline (0.5 mg/kg, i.p., non-selective adenosine receptor antagonist) and 8-cyclopentyl-1,3-dipropylxanthine (5 mg/kg, i.p., adenosine A1 receptor antagonist) but not by 8-(3-cholorostryl)caffeine (4 mg/kg, i.p., adenosine A2A receptor antagonist). Further, 5'-N-ethylcarboxamidoadenosine (0.005 mg/kg, i.p., non-selective A1 /A2 receptor agonist), or N(6) -cyclohexyladenosine (0.2 mg/kg, i.p., adenosine A1 receptor agonist), was able to potentiate the anticonvulsant action of curcumin. In contrast, 5'-(N-cyclopropyl) carboxamidoadenosine (0.1 mg/kg, i.p., adenosine A2A receptor agonist) failed to potentiate the effect of curcumin. This study demonstrated the anticonvulsant effect of curcumin against PTZ i.v. seizure threshold via a direct or indirect activation of adenosine A1 but not A2A receptors in mice. Thus, curcumin may prove to be an effective adjunct in treatment of convulsions.