Serine/threonine protein phosphatases have no role in the inhibitory effects of low-frequency stimulation in perforant path kindling acquisition in rats

The use of low-frequency stimulation (LFS) as a therapy for epilepsy is currently being studied in experimental animals and patients with epilepsy. In the present study, the role of serine/threonine protein phosphatases in the inhibitory effects of LFS on perforant path kindling acquisition was investigated in rats. Animals were kindled by stimulation of perforant path in a stimulation using rapid kindling procedure (six stimulations per day). LFS (1Hz) was applied immediately after termination of each kindling stimulation. FK506 (1microM; i.c.v.), a serine/threonine protein phosphatase PP2B inhibitor and okadaic acid (1microM; i.c.v.), a serine/threonine protein phosphatases PP1/2A inhibitor, were daily microinjected into the left ventricle 10min before starting the stimulation protocol. Application of LFS retarded the kindling acquisition and delayed the expression of different kindled seizure stages significantly. In addition, LFS reduced the increment of daily afterdischarge duration during kindling development. Neither FK506 nor okadaic acid microinjection interfere with the antiepileptogenic effect of LFS on kindling parameters. Obtained results showed that activation of PP1/2A and PP2B, which play a critical role in LFS induced down-regulation of synaptic strength, had no role in mediating the inhibitory effects of LFS on perforant path kindling acquisition.