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 (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.
Psarropoulou
C
C
Department of Physiology, Medical School, University of Patras, Greece.
Matsokis
N
N
Angelatou
F
F
Kostopoulos
G
G
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007696:Kindling, Neurologic / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010433:Pentylenetetrazole; D018079:Receptors, GABA / Q000187:drug effects; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D009435:Synaptic Transmission / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018079:Receptors, GABA; D018047:Receptors, Purinergic P1; D005680:gamma-Aminobutyric Acid; D000241:Adenosine; D010433:Pentylenetetrazole