Dr. Psarropoulou's present address is Montreal Neurological Institute, 3801 University St., Montreal, Quebec H3A2B4, Canada.
Pentylenetetrazol-Induced Seizures Decrease γ-Aminobutyric Acid-Mediated Recurrent Inhibition and Enhance Adenosine-Mediated Depression
Article first published online: 20 SEP 2006
Volume 35, Issue 1, pages 12–19, January 1994
How to Cite
Psarropoulou, C., Matsokis, N., Angelatou, F. and Kostopoulos, G. (1994), Pentylenetetrazol-Induced Seizures Decrease γ-Aminobutyric Acid-Mediated Recurrent Inhibition and Enhance Adenosine-Mediated Depression. Epilepsia, 35: 12–19. doi: 10.1111/j.1528-1157.1994.tb02906.x
- Issue published online: 20 SEP 2006
- Article first published online: 20 SEP 2006
- Received August 1992; revision accepted January 1993.
- Neurologic models;
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 μM 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 (Bmax 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.