Pentylenetetrazol-Induced Seizures Decrease γ-Aminobutyric Acid-Mediated Recurrent Inhibition and Enhance Adenosine-Mediated Depression

Summary: To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonicclonic 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 CAI 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 γ-aminobutyric acid, (GABA)-mediated recurrent inhibition was significantly weaker (by 19–25%) in the CA1 area of slices from PTZtreated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABA, 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 μ 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 A₁ receptor density in hippocampus ( B _max of ³H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A₁-mediated adaptive mechanism that offers protection from subsequent seizures.