Reduction of paired pulse inhibition in the CA1 region of the hippocampus by pilocarpine in naive and in amygdala-kindled rats

Abstract

Subconvulsant doses (20 mg/kg) of pilocarpine administered to a kindled rat convert a kindled seizure to status epilepticus. The hippocampus is involved in such status epilepticus. Furthermore, evidence is accumulating that GABA-mediated inhibition in the hippocampus is chronically diminished by kindling. The studies presented here compared the electrophysiologic effects of pilocarpine in vivo in the CA1 region of the hippocampus in naive and amygdala-kindled rats. A paired pulse paradigm previously shown to quantify the potency of GABAergic inhibition was employed. Stimuli were delivered to the CA3 region of urethane-anesthetized rats and population spikes were recorded in the contralateral CA1 region. In naive rats, pilocarpine (6–60 mg/kg) caused a left shift in the input-output curve measuring stimulus intensity vs population spike amplitudes, indicating an increase in neuronal excitability. In addition, paired pulse inhibition was reduced for interpulse intervals < 70 ms. In amygdala-kindled rats, neuronal excitability was also enhanced following pilocarpine administration. The potency of baseline paired pulse inhibition was decreased in kindled rats compared to naive controls. Following pilocarpine, inhibition for interpulse intervals < 70 ms was further reduced, but to a lesser extent than in naive rats. These findings suggest that the ability of subconvulsive doses of pilocarpine to change a discrete kindled seizure triggered by one stimulus to status epilepticus depends on the suppression of GABAergic inhibition below a critical level.