Altered N-methyl-d-aspartate (NMDA) activity in the mouse spinal cord following morphine is mediated by sigma activity

Julie S. Kreeger, Rustam Yu Yukhananov, Alice A. Larson

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The present study was designed to determine whether the increase in N-methyl-d-aspartate (NMDA) activity in the mouse spinal cord, unmasked by naloxone in morphine-pretreated mice, is mediated by sigma receptor activity. Behavioral responses to intrathecal injections of NMDA were inhibited by pretreatment (2 h) with morphine (10 mg/kg i.p.) except when NMDA was injected together with 0.1 μg of naloxone. This excitatory effect of morphine on NMDA-induced behaviors, unmasked in the presence of naloxone was prevented but not reversed by haloperidol, a sigma ligand and dopamine antagonist, but not by an equivalent dose of spiperone, a dopamine antagonist. Sigma activity also appeared to contribute to morphine withdrawal jumping in mice as haloperidol inhibited naloxone-induced jumping while spiperone did not. Together these data indicate that naloxone unmasks an action of morphine on NMDA and during acute withdrawal, and these effects are each brought about by mechanisms involving sigma receptor activity.

Original languageEnglish (US)
Pages (from-to)83-88
Number of pages6
JournalBrain Research
Volume672
Issue number1-2
DOIs
StatePublished - Feb 20 1995

Keywords

  • Dependence
  • Haloperidol
  • MK-801
  • Morphine
  • NMDA
  • Withdrawal

Fingerprint Dive into the research topics of 'Altered N-methyl-d-aspartate (NMDA) activity in the mouse spinal cord following morphine is mediated by sigma activity'. Together they form a unique fingerprint.

  • Cite this