TY - JOUR
T1 - Opioid antinociception, tolerance and dependence
T2 - Interactions with the N-methyl-D-aspartate system in mice
AU - Dykstra, Linda A.
AU - Fischer, Bradford D.
AU - Balter, Rebecca E.
AU - Henry, Fredrick E.
AU - Schmidt, Karl T.
AU - Miller, Laurence L.
PY - 2011/9
Y1 - 2011/9
N2 - This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10%, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3- carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.
AB - This study explored the involvement of N-methyl-D-aspartate (NMDA) in the effects of μ-opioid agonists. A hot-plate procedure was used to assess antinociception and tolerance in mice in which the NR1 subunit of the NMDA receptor was reduced [knockdown (KD)] to approximately 10%, and in mice treated with the NMDA antagonist, (-)-6-phosphonomethyl-deca-hydroisoquinoline-3- carboxylic acid (LY235959). The μ opioid agonists, morphine, l-methadone and fentanyl, were approximately three-fold less potent in the NR1 KD mice than in wild-type (WT) controls; however, the development of morphine tolerance and dependence did not differ markedly in the NR1 KD and the WT mice. Acute administration of the NMDA antagonist, LY235959, produced dose-dependent, leftward shifts in the morphine dose-effect curve in the WT mice, but not in the NR1 KD mice. Chronic administration of LY235959 during the morphine tolerance regimen did not attenuate the development of tolerance in the NR1 KD or the WT mice. These results indicate that the NR1 subunit of the NMDA receptor does not play a prominent role in μ opioid tolerance.
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UR - http://www.scopus.com/inward/citedby.url?scp=80051942769&partnerID=8YFLogxK
U2 - 10.1097/FBP.0b013e328348ed08
DO - 10.1097/FBP.0b013e328348ed08
M3 - Article
C2 - 21712708
AN - SCOPUS:80051942769
SN - 0955-8810
VL - 22
SP - 540
EP - 547
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
IS - 5-6
ER -