PICROTOXIN-INDUCED BEHAVIORAL TOLERANCE AND ALTERED SUSCEPTIBILITY TOSEIZURES - EFFECTS OF NALOXONE

The role of opiate mechanisms in the development of tolerance and alte red susceptibility to seizures after repeated injections of picrotoxin was investigated. Independent groups of rats were pretreated with nal oxone (0.3, 1.0, 3.0, and 10.0 mg/kg) or the saline vehicle and then t ested for seizures induced by picrotoxin. The procedure was performed on 3 days at 1-week intervals, for a total of 3 testing days. Latencie s to different types of seizures, the duration of postseizure immobili ty, and the number of focal seizure episodes were scored. In the vehic le-treated group, repeated picrotoxin injections led to an increased s usceptibility to myoclonic and focal seizures and to decreased duratio n of postseizure immobility. Naloxone pretreatment significantly decre ased the duration of the postseizure akinetic periods in the 1.0- and 10.0-mg/kg groups across all days, suggesting that endogenous opiates are involved in postseizure immobility and that there are interactions between opiate and picrotoxin mechanisms in some seizure-related beha viors. Naloxone did not alter the development of tolerance or sensitiv ity, indicating that naloxone-insensitive opiate mechanisms or nonopia te mechanisms may be involved in these processes.