Effects of dizocilpine in Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice

John Jr Crabbe, Emmett R. Young, Janet Dorow

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Mice selectively bred to be Withdrawal Seizure-Prone (WSP) or Seizure-Resistant (WSR) after chronic ethanol administration have been reported to be differentially sensitive to the anticonvulsant and proconvulsant effects on alcohol withdrawal of drugs interacting with glutamate receptors. Several behavioral effects of the noncompetitive glutamate receptor antagonist, dizocilpine, were determined in WSP and WSR mice to see whether their differential sensitivity generalized to effects unrelated to seizures, and to see whether it was only apparent during ethanol withdrawal. Dizocilpine potentiated the loss of righting reflex induced by ethanol, and dose-dependently stimulated habituated and nonhabituated open field activity. WSP and WSR mice were equally sensitive to these effects of dizocilpine. Pretreatment with dizocilpine increased the transcorneal amperage necessary to produce maximal electroshock seizures: WSR mice were more sensitive than WSP to this effect. Ethanol withdrawal (i.e., testing 6 h after a 24-h exposure to ethanol vapor) and dizocilpine had several effects on mice tested in the hole-in-wall apparatus. Several differences between WSP and WSR mice were also found, but in no case did dizocilpine differentially affect ethanol-withdrawing WSP and WSR mice. Across these experiments, differences between WSP and WSR mice in response to dizocilpine were rather specific. For some responses, WSP and WSR mice were equally sensitive, but only in the seizure-related measure assessed were naive WSR mice more sensitive than WSP. Since naive WSR mice are also more sensitive to NMDA-induced convulsions than WSP, these data are consistent with the hypothesis that alterations in the function of excitatory amino acid-gated ion channels are important for the convulsions accompanying withdrawal from ethanol dependence.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalPharmacology, Biochemistry and Behavior
Volume47
Issue number3
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Dizocilpine Maleate
Seizures
Ethanol
Excitatory Amino Acid Antagonists
Excitatory Amino Acids
Glutamate Receptors
N-Methylaspartate
Ion Channels
Anticonvulsants
Vapors
Alcohols
Testing
Pharmaceutical Preparations

Keywords

  • Anticonvulsant
  • Dizocilpine
  • Ethanol withdrawal
  • Excitatory amino acids
  • MK-801
  • Pharmacogenetics
  • Seizures
  • Selected mouse lines
  • WSP
  • WSR

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Effects of dizocilpine in Withdrawal Seizure-Prone (WSP) and Withdrawal Seizure-Resistant (WSR) mice. / Crabbe, John Jr; Young, Emmett R.; Dorow, Janet.

In: Pharmacology, Biochemistry and Behavior, Vol. 47, No. 3, 1994, p. 443-450.

Research output: Contribution to journalArticle

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