Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine-mediated depression

• Published in: Epilepsia (Copenhagen) Vol. 35; no. 1; p. 12
• Main Authors: Psarropoulou, C, Matsokis, N, Angelatou, F, Kostopoulos, G
• Format: Journal Article
• Language: English
• Published: United States 01.01.1994
• Subjects: Action Potentials - drug effects; Adenosine - physiology; Animals; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Down-Regulation - drug effects; Electric Stimulation; Female; gamma-Aminobutyric Acid - physiology; Hippocampus - drug effects; Hippocampus - physiology; Kindling, Neurologic - physiology; Mice; Mice, Inbred BALB C; Pentylenetetrazole; Receptors, GABA - drug effects; Receptors, Purinergic P1 - drug effects; Seizures - chemically induced; Synaptic Transmission - drug effects; Up-Regulation - drug effects
• ISSN: 0013-9580
• DOI: 10.1111/j.1528-1157.1994.tb02906.x

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 (GABAA)-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CA1 area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABAA 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 microM 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.