EFFECTS OF DIZOCILPINE IN WITHDRAWAL SEIZURE-PRONE (WSP) AND WITHDRAWAL SEIZURE-RESISTANT (WSR) MICE

Mice selectively bred to be Withdrawal Seizure-Prone (WSP) or Seizure- Resistant (WSR) after chronic ethanol administration have been reporte d to be differentially sensitive to the anticonvulsant and proconvulsa nt effects on alcohol withdrawal of drugs interacting with glutamate r eceptors. Several behavioral effects of the noncompetitive glutamate r eceptor antagonist, dizocilpine, were determined in WSP and WSR mice t o see whether their differential sensitivity generalized to effects un related to seizures, and to see whether it was only apparent during et hanol withdrawal. Dizocilpine potentiated the loss of righting reflex induced by ethanol, and dose-dependently stimulated habituated and non habituated open field activity. WSP and WSR mice were equally sensitiv e to these effects of dizocilpine. Pretreatment with dizocilpine incre ased the transcorneal amperage necessary to produce maximal electrosho ck seizures: WSR mice were more sensitive than WSP to this effect. Eth anol withdrawal (i.e., testing 6 h after a 24-h exposure to ethanol va por) and dizocilpine had several effects on mice tested in the hole-in -wall apparatus. Several differences between WSP and WSR mice were als o found, but in no case did dizocilpine differentially affect ethanol- withdrawing WSP and WSR mice. Across these experiments, differences be tween WSP and WSR mice in response to dizocilpine were rather specific . For some responses, WSP and WSR mice were equally sensitive, but onl y in the seizure-related measure assessed were naive WSR mice more sen sitive than WSP. Since naive WSR mice are also more sensitive to NMDA- induced convulsions than WSP, these data are consistent with the hypot hesis that alterations in the function of excitatory amino acid-gated ion channels are important for the convulsions accompanying withdrawal from ethanol dependence.