PENTYLENETETRAZOL-INDUCED SEIZURES DECREASE GAMMA-AMINOBUTYRIC ACID-MEDIATED RECURRENT INHIBITION AND ENHANCE ADENOSINE-MEDIATED DEPRESSION

To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CA1 area of hippocampal slices showed that PTZ-induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired-pulse stimulation paradigm showed that gamma-aminobutyric acid(A) (GABA(A))-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CAI area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABA(A) receptors (high-affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 mu M on the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A(1) receptor density in hippocampus (B-max of [H-3]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A(1)-mediated adaptive mechanism that offers protection from subsequent seizures.