Pharmacological characterization of the afterdischarge that precedes the onset of maximal dentate activation in the rat

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Two types of afterdischarges have been recorded in the dentate gyrus after trains of electrical stimulation. The first afterdischarge contains predominantly broad positive potentials. The second afterdischarge contains bursts of large amplitude population spikes and has been termed maximal dentate activation. It has been proposed that the first afterdischarge is a precursor to maximal dentate activation and, therefore, it is termed a pre-MDA afterdischarge. The effects of several drugs on these afterdischarges were compared in adult male rats anesthetized with urethane. Stimulus trains (50 Hz) designed to elicit the pre-MDA afterdischarge were administered to the left CA3 region while recording in the ipsilateral dentate gyrus and contralateral CA1 cell layer. Phenytoin (80 mg kg ), phenobarbital (60 mg kg ), ethosuximide (300 mg kg ) and sodium valproate (300 mg kg ) had no effect on the duration or characteristics of the discharge. Carbamazepine (50–60 mg/kg) and ketamine (30 mg kg ) reversibly blocked the discharge. Diazepam (3 mg kg ) reduced the duration of the discharge and also reduced the amplitude of population spikes recorded in CA1. Baclofen (10 mg kg ) and bicuculline (0.5 mg kg ) increased the duration of the discharge. The effects of dizocilpine (MK-801, 2 mg kg ) were inconsistent. These results were compared to the effects of the same drugs on the time-to-onset and duration of maximal dentate activation. The pharmacological sensitivities of maximal dentate activation and pre-MDA discharges were found to be qualitatively different.