title: NMDA receptor antagonists inhibit opiate antinociceptive tolerance and locomotor sensitization in rats.
abstract: BACKGROUND
  N-Methyl-D: -aspartate (NMDA) receptors have an important role in different forms of behavioral and neural plasticity. Evidence suggests that these receptors may also be involved in plasticity arising from long-term treatment with different drugs of abuse, including tolerance, sensitization, and physical dependence. There is abundant evidence demonstrating that NMDA receptors are involved in tolerance to opiate-induced antinociception; however, the role of these receptors in sensitization to the locomotor effects of opiates is more controversial.
  
  
  OBJECTIVE
  The ability of NMDA receptor antagonists to modify the development of sensitization to the locomotor stimulant effect of three different opiates was examined. In selected studies, the ability of the antagonists to modify tolerance to the antinociceptive effects of the opiates was also examined.
  
  
  METHODS
  Adult male Sprague-Dawley rats were used to assess the effects of NMDA receptor antagonists (MK-801, memantine or LY235959) on tolerance and sensitization to three opiates: morphine, methadone, or buprenorphine. It was predicted that low, selective doses of the antagonists would inhibit the development of opiate tolerance and sensitization.
  
  
  RESULTS
  Consistent with our predictions, the noncompetitive NMDA receptor antagonists MK-801 and memantine and the competitive NMDA receptor antagonist LY235959 inhibited the development of sensitization to the locomotor stimulant effect of morphine. Additionally, MK-801 inhibited the development of tolerance and sensitization to methadone and buprenorphine in a similar manner.
  
  
  CONCLUSIONS
  The results, together with previous research, suggest that NMDA receptors are broadly involved in opiate-induced plasticity, including the development of opiate tolerance and sensitization.
authors.affiliation: Department of Psychology, Texas A & M University, College Station, TX 77843, USA. mend251@tamu.edu
authors.forename: Ian A
authors.initials: IA
authors.lastname: Mendez
authors.forename: Keith A
authors.initials: KA
authors.lastname: Trujillo
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004361:Drug Tolerance / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D008691:Methadone / Q000008:administration & dosage / Q000494:pharmacology; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009293:Opioid-Related Disorders; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D009294:Narcotics; D016194:Receptors, N-Methyl-D-Aspartate; D002047:Buprenorphine; D016291:Dizocilpine Maleate; D009020:Morphine; C088643:LY 235959; D008691:Methadone; D008559:Memantine