Sensitization to noise-mediated induction of seizure susceptibility by MK-801 and phencyclidine

The effect of single administrations of MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) or PCP (phencyclidine) on the induction of audiogenic seizure susceptibility by noise in immature rats was examined. Treatments with these non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists resulted in increases in noise exposure-dependent susceptibility. In neonatally drug-treated rats, seizures during adulthood were found to occur with significantly higher incidence and severity. Furthermore, drug treatments were found to lengthen what is normally a restricted developmental period within which susceptibility can be induced by noise exposure. The drugs, however, had no inherent ability to induce audiogenic seizure susceptibility if given alone. Moreover, in already-susceptible rats, MK-801 exhibited predictable anticonvulsant effects. These data suggest acute PCP or MK-801 exposures may transiently exacerbate risks inherent in certain forms of trauma. The mechanism underlying these effects is unknown although certain inferences are possible and may reveal much about epileptogenesis in this model.