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

To elucidate the consequences of convulsions, we examined biochemicall y and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenete trazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before deca pitation. 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 persiste nt change in hippocampal excitability itself that can be detected in v itro. However, use of the paired-pulse stimulation paradigm showed tha t gamma-aminobutyric acid(A) (GABA(A))-mediated recurrent inhibition w as 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 compo nent) was also lower in hippocampus (by 19%) and cortex (by 14%) of PT Z-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing th e brain to subsequent seizures. On the other hand, the depressant effe ct 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 s lices as compared with controls. This could be attributed to significa ntly 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 a nimals. The phenomenon may reflect an adenosine A(1)-mediated adaptive mechanism that offers protection from subsequent seizures.