Studies have shown that adenosine analogs may modulate kindled seizures. The present study demonstrated that systemic administration of the adenosine analog, l-phenylisopropyladenosine (l-PIA), substantially prolonged the postictal depression and decreased the frequency of spiking that follows amygdala-kindled seizures in rats. Fully kindled rats were administered l-PIA (0.1 to 2.0 mg/kg, i.p.) or saline 30 min before stimulation of the amygdala. Afterdischarge durations with l-PIA did not differ from those with saline, and behavioral seizures were only slightly decreased in severity with 2.0 mg/kg l-PIA. However, 0.5 to 2.0 mg/kg l-PIA increased the duration of the postictal depression by more than 20 min and, at 2.0 mg/kg, l-PIA decreased the frequency of postictal spiking. Postictal administration of caffeine (32 mg/kg, i.p.) reversed the prolongation of the postictal depression induced by 1.0 mg/kg l-PIA. These effects did not seem to be mediated by peripheral actions of l-PIA (i.e., lowered blood pressure) as hydralazine, which decreases blood pressure through peripheral mechanisms, did not affect ictal or postictal events. These results indicate that adenosine may modulate neuronal excitability that follows kindled seizures.
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