Blockade of the polyamine site of NMDA receptors produces antinociception and enhances the effect of morphine, in mice

Bernardi, M.; Bertolini, Alfio; Szczawińska, K; Genedani, Susanna

doi:10.1016/0014-2999(95)00778-4

Cited by 51 publications

(26 citation statements)

References 36 publications

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“…However, the present results also differ from other studies that evaluated the effect of NR2B receptor antagonism in morphine analgesia [3,9]. Those studies showed that antagonism of NR2B receptors increase the analgesic effects of morphine on phasic pain tests [3,9]. It can be appreciated that there is a high degree of variability in the effects of NMDA antagonists on morphine analgesia, as some studies have shown potentiation, whereas other studies attenuation or no effect [3,9,19,20,27,32].…”

contrasting

confidence: 99%

“…For instance, dextromethorphan (a low affinity and non competitive antagonist) attenuates morphine analgesia at high dose, and the polyamine NR2B antagonist Ro 25-6981 attenuates morphine analgesia at all doses examined [27]. However, the present results also differ from other studies that evaluated the effect of NR2B receptor antagonism in morphine analgesia [3,9]. Those studies showed that antagonism of NR2B receptors increase the analgesic effects of morphine on phasic pain tests [3,9].…”

contrasting

confidence: 97%

“…Specifically, Fischer et al [9] reported in adult male C57BL/6 mice that antagonism of NR2B by ifenprodil (dose of 10mg/kg) increased significantly the analgesic effect of morphine (doses of 1mg/kg, 3.2mg/kg and 10mg/kg) in the hot plate test. Similarly, another study in adult male Swiss Albino mice [3] showed that antagonism of NR2B by ifenprodil (dose of 30mg/kg) enhance the antinociceptive effect of morphine (dose of 5mg/kg) in the hot plate test.…”

mentioning

confidence: 82%

“…NIH-PA Author Manuscript NIH-PA Author Manuscript effect of NR2B receptor antagonism in morphine analgesia [3,9]. Those studies showed that antagonism of NR2B receptors increase the analgesic effects of morphine on phasic pain tests [3,9].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…Previous studies on the role of NMDA receptors subunits in morphine analgesia have shown that antagonism of NR2B receptors increase the analgesic effects of morphine on phasic pain conditions [3,9]. Specifically, Fischer et al [9] reported in adult male C57BL/6 mice that antagonism of NR2B by ifenprodil (dose of 10mg/kg) increased significantly the analgesic effect of morphine (doses of 1mg/kg, 3.2mg/kg and 10mg/kg) in the hot plate test.…”

mentioning

confidence: 99%

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Evaluation of morphine analgesia and motor coordination in mice following cortex-specific knockout of the N-methyl-d-aspartate NR1-subunit

Quintero

Erzurumlu

Vaccarino

2008

Neuroscience Letters

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Studies have shown that N-methyl-D-Aspartate (NMDA) receptors play a critical role in morphine analgesia and motoric processes at different levels of the central nervous system. In this study, we used cortex specific NR1 knockout mice (C57BL/6 strain) to elucidate the role of cortical NMDA receptors in morphine analgesia and motor coordination. On post-natal day 20, mice (CTL and KO) received vehicle (saline) or morphine (10mg/kg) and paw withdrawal latency (PWL) to a noxious thermal stimulus was measured. On post-natal day 21, motor coordination was measured using the rotating pole test. No differences in KO mice were found with respect to PWL following administration of saline or morphine (p > 0.05). However, sex-dependent differences were in motor coordination, with male KO mice showing a greater motor impairment in the rotating pole test than female KO mice (p < 0.05). The present results demonstrate that NMDA receptors are involved in both the analgesic effects of morphine and motor coordination, with the existence of sex-related differences in motor coordination. KeywordsMotor coordination; morphine; analgesia; NMDA receptor; knockout; Noxious thermal stimuli N-methyl-D-Aspartate (NMDA) receptors are hetero-oligomers ligand-gated ion channel that interacts with diverse intracellular proteins [26], composed of subunits NR1, NR2 (A,B,C,D) and NR3 (A,B) [8,26]. Functionally, NMDA receptors are involved in coordinating motor responses [4,5,28], and are suggested to play a critical role in mediating pain and analgesia [29], including the analgesic effects of morphine [13,19,20,27].The present study was designed to elucidate further the role of NMDA receptors in mediating morphine analgesia and motor coordination by using NR1 -NMDA cortex-specific KO mice * Corresponding author at: Department of Psychology, University of New Orleans, New Orleans, Louisiana 70148, U.S. A., Tel: 504-280-1212; Fax: 504-280-6049., E-mail address: gaboquintero2006@yahoo.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. KO [21] reported that these mice die at perinatal stage, being not possible to evaluate morphine analgesia and motor coordination aspects. NIH Public AccessWestern blot and in situ hybridization analysis reveals that, as compared with controls, NR1 -NMDA cortex-specific KO mice have a 95% reduction of NR1 subunit levels in cortex and hippocampus [12]. Using x-gal staining, the spatial restriction of Cre recombination has been verified at cortical levels [12]. Cortex-specific NR1 KO mice were originally generated by Iwasato et al. [12] by inserting the Cre recombin...

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