Behavioral sensitization to ethanol does not result in cross-sensitization to NMDA receptor antagonists

Paul J. Meyer, Tamara J. Phillips

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Rationale: Behavioral sensitization to the locomotor stimulant effects of ethanol may be related to neuroadaptations within glutamatergic systems. Previous research has suggested that the N-methyl-d-aspartate (NMDA) subclass of glutamate receptors is critical for the development of ethanol sensitization. We hypothesized that sensitization to ethanol would be associated with changes in sensitivity to NMDA receptor ligands. Materials and methods: DBA/2J and heterogeneous stock (HS) mice were injected with ethanol or saline for 12 days and tested for their acute and sensitized responses to the locomotor effects of ethanol in automated activity monitors. After this treatment phase, mice were challenged with MK-801, ethanol, or ketamine, and locomotor activity was measured for 20 to 60 min. Other ethanol-sensitized and nonsensitized mice were assessed for sensitivity to the effects of NMDA after tail-vein infusions. Results: There was no evidence for cross-sensitization to MK-801 or ketamine, or altered sensitivity to NMDA in ethanol-sensitized animals, in any experiment. In one experiment, previously ethanol-treated HS mice developed tolerance to the locomotor stimulant effects of ketamine. Conclusions: These results indicate that ethanol-induced behavioral sensitization is not associated with increased behavioral sensitivity to NMDA receptor antagonists or altered sensitivity to NMDA receptor agonists. To the extent that changes in sensitivity to these ligands reflect changes in NMDA receptors, these results are inconsistent with the hypothesis that ethanol sensitization is associated with alterations in NMDA receptor-mediated processes.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalPsychopharmacology
Volume195
Issue number1
DOIs
StatePublished - Nov 1 2007

Keywords

  • Activation
  • Adaptation
  • Addiction
  • Alcohol
  • Drug abuse
  • Excitatory amino acid
  • Glutamate receptor
  • Motor activity
  • Psychostimulant
  • Reverse tolerance

ASJC Scopus subject areas

  • Pharmacology

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