cAMP-dependent protein kinase (PKA) is a major modulator of synaptic transmission likely to be involved in molecular and cellular events leading to epileptogenesis, but little is known about how it affects the onset of acute epileptic
seizures. In this study, we determined PKA enzymatic activity in the rat hippocampus during
picrotoxin-induced
seizures, using
H-9 dihydrochloride, a
PKA inhibitor, to investigate the in vivo effects of this
enzyme on
seizures induced by
picrotoxin microdialysis in the rat hippocampus. No significant modifications were found in PKA activity during
seizures as compared to control rats, but
H-9 dihydrochloride microperfusion (100 microM) prevented
picrotoxin seizures in 50% of the animals and significantly reduced the mean number of
seizures and mean seizure duration. These results suggest that acute
picrotoxin-induced
seizures occur without an increase in hippocampal PKA activity, but reduced PKA-mediated phosphorylation protects against
picrotoxin seizures, probably by increasing the inhibitory potential of
GABA(A) receptors. The possibility of other targets for
H-9 dihydrochloride, such as PKC, PKG or
CAMKII, however, cannot be ruled out.