Phencyclidine inhibition of the rate of development of amygdaloid kindled seizures

Administration of (5, 10, 20 or 35 mg/kg, i.p.) phencyclidine (PCP) 15 min prior to each stimulation significantly reduced the rate of kindling induced by daily electrical stimulation of the amygdala in the rat. All four doses significantly reduced the rate of kindling measured by the behavioral ranking (BR) and the afterdischarge duration (AD). The drug at 2.5 mg/kg had no significant effect on the rate of kindling. The 20- and 35-mg/kg PCP doses significantly reduced the afterdischarge duration evoked by the first stimulation to 40.2 ± 16.1% and 13.5 ± 9.2% (mean ± se) of the control value. The 5- and 10-mg/kg doses reduced the initial AD to approximately 65% of control. After switching from PCP to normal saline all rats kindled. The 5-mg/kg group which was injected 12 days with PCP required 15.0 ± 0.9 stimulations to develop a maximal BR whereas the control group required only 10.2 ± 0.5 stimulations. The saline controls were injected with 5 mg/kg PCP after their BR was maximal. This dose minimally reduced the AD to 88.8 ± 6.8% of the previous two stimulations and had no effect on the BR. It is apparent that 5 mg/kg PCP will inhibit the initial afterdischarge and the rate of kindling while minimally affecting fully kindled seizure activity. Naloxone at 6 mg/kg failed to reverse the inhibition of the rate of kindling produced by 5 mg/kg PCP daily. Neither 5 mg/kg morphine, an opiate agonist, nor 5 mg/kg quipazine, a serotonergic agonist, significantly affected the rate of kindling in similar experiments. Pretreatment of rats with 10 or 20 mg/kg PCP once daily for 4 days prior to the beginning of daily kindling stimulations did not affect the rate of kindling.