The NMDA receptor antagonist MK-801 prevents long-lasting non-associative morphine tolerance in the rat

Ben‐Eliyahu, Shamgar; Marek, Przemysław; Vaccarino, Anthony L.; Mogil, Jeffrey S.; Sternberg, Wendy F.; Liebeskind, John C.

doi:10.1016/0006-8993(92)90094-p

Cited by 137 publications

(57 citation statements)

References 16 publications

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“…4 Likewise, a growing body of evidence indicates that pronociceptive processes associated with central sensitization are associated primarily with amino acid activity at the NMDA receptor level, [8][9][10] and studies have shown that opioid induced hyperalgesia is prevented by the NMDA receptor antagonists ketamine and MK-801. 4,17,18 This is in accordance with previous studies which demonstrate that opioid-induced central sensitization and neuropathic pain share common pathophysiologic mechanisms. 6,7 On the other hand, Begon et al have shown in a preclinical study in rats that systemic magnesium and systemic MK-801 similarly reverse mechanical hyperalgesia in diabetic and mono-neuropathic rats.…”

Section: Discussionsupporting

confidence: 92%

Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats

et al. 2006

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Section: Discussionsupporting

confidence: 92%

Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats

et al. 2006

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“…Recent behavioral studies have indicated a critical role for the NMDA receptor in the development of morphine tolerance and dependence (Marek et al, 199 la,b;Tanganelli et al, 1991;Trujillo and Akil, 199 1;Ben Eliyahu et al, 1992). The site of the NMDA receptor action is likely within the spinal cord since spinalization does not diminish the preventive effect of systemic MK 801 on the development of morphine tolerance (Gutstein et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

“…Ofrelevant interest is that investigations on narcotic tolerance and dependence have indicated that the NMDA receptor activation also plays a critically important role in the development of narcotic tolerance and dependence, since MK 801, a noncompetitive NMDA receptor antagonist, has been shown to prevent the development of morphine tolerance and dependence in several experimental models (Marek et al, 199 la,b;Tanganelli et al, 1991;Trujillo and Akil, 1991;Ben Eliyahu et al, 1992). The site ofthe NMDA receptor activation is likely within the spinal cord, because spinalization does not reverse the inhibition of the development of morphine tolerance by systemic MK 801 administration (Gutstein et al, 1992).…”

mentioning

confidence: 99%

Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C

1994

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In a rat model of morphine tolerance, we examined the hypotheses that thermal hyperalgesia to radiant heat develops in association with the development of morphine tolerance and that both the development and expression of thermal hyperalgesia in morphine-tolerant rats are mediated by central NMDA and non-NMDA receptors and subsequent protein kinase C (PKC) activation. Tolerance to the analgesic effect of morphine was developed in rats utilizing an intrathecal repeated treatment regimen. The development of morphine tolerance and thermal hyperalgesia was examined by employing the tail-flick test and paw- withdrawal test, respectively. Intrathecal MK 801 (an NMDA receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; a non-NMDA receptor antagonist), or GM1 ganglioside (an intracellular PKC inhibitor) treatment was given to examine the effects of these agents on the development and expression of thermal hyperalgesia in morphine- tolerant rats. Tolerance to the analgesic effect of morphine was reliably developed in rats following once daily intrathecal (onto the lumbosacral spinal cord) injection of 10 micrograms of morphine sulfate for 8 consecutive days as demonstrated by the decreased analgesia following morphine administration on day 8 as compared to that on day 1. In association with the development of morphine tolerance, thermal hyperalgesia to radiant heat developed in these same rats. Paw- withdrawal latencies were reliably decreased in morphine-tolerant rats as compared to nontolerant (saline) controls when tested on day 8 before the last morphine treatment and on day 10 (i.e., 48 hr after the last morphine treatment). The coincident development of morphine tolerance and thermal hyperalgesia was potently prevented by intrathecal coadministration of morphine with MK 801 (10 nmol) or GM1 (160 nmol), and partially by CNQX (80 nmol). MK 801 (5, 10 nmol, not 2.5 nmol) and CNQX (80, 160 nmol, not 40 nmol), but not GM1 (160 nmol), also reliably reversed thermal hyperalgesia in rats rendered tolerant to morphine when tested 30 min after each drug treatment on day 10 (48 hr after the last morphine treatment). The data indicate that thermal hyperalgesia develops in association with the development of morphine tolerance and that the coactivation of central NMDA and non-NMDA receptors is crucial for both the development and expression of thermal hyperalgesia in morphine-tolerant rats. Furthermore, intracellular PKC activation plays a critical role in the development of thermal hyperalgesia in morphine-tolerant rats.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The functional association between MOR and NMDA receptor ligands is further supported by observations in opiate addiction paradigms. Tolerance and withdrawal symptoms, for example, are both prevented by the administration of MOR or NMDA receptor antagonists (Gulya et al, 1988;Ben-Eliyahu et al, 1992;Kolesnikov et al, 1993;Trujillo and Akil, 1994). Opiate self-administration is also blocked by lesioning the Acb (Zito et al, 1985), providing further evidence that this region is involved in the motivational and withdrawal aspects of opiate addiction (Olds, 1982;Goeders et al, 1984;Koob et al, 1989).…”

Section: Abstract: Opiate; Withdrawal; Locomotion; Addiction; Glutammentioning

confidence: 94%

Dual Ultrastructural Localization of μ-Opioid Receptors and NMDA-Type Glutamate Receptors in the Shell of the Rat Nucleus Accumbens

1997

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The effectiveness of NMDA antagonists in modulating the motor and motivational effects of opiates is attributed, in part, to functional associations involving NMDA receptors and -opioid receptors (MORs) in the shell of the nucleus accumbens (Acb). To determine the subcellular sites for potential functional interactions between opiate ligands and NMDA receptors in this region, we examined the ultrastructural localization of antipeptide antisera against MOR and the R1 subunit of the NMDA receptor in the Acb shell of the adult rat brain. MOR-like immunoreactivity (MOR-LI) was seen primarily in dendrites, whereas NMDAR1-like immunoreactivity (NMDAR1-LI) was detected more often in axon terminals forming asymmetric synapses. In these profiles, MOR labeling was localized mainly to extrasynaptic plasma membranes, whereas NMDAR1-LI was associated with both synaptic and extrasynaptic sites. Of 307 MOR-labeled processes, 17.9% of the dendrites and 9.4% of the axon terminals also contained NMDAR1-LI. In addition, 24.7% of the dendrites containing only MOR-LI were apposed to NMDAR1-labeled axons or terminals. We conclude that in the shell of the Acb, the output of single neurons can be dually modulated by (1) activation of MOR and NMDA receptors in the same dendrites or (2) combined activation of presynaptic NMDA receptors in afferents contacting dendrites containing MOR. In addition, the colocalization of MOR and NMDAR1 in certain axon terminals in the Acb suggests their dual involvement in the presynaptic release of neurotransmitters in this region.

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The NMDA receptor antagonist MK-801 prevents long-lasting non-associative morphine tolerance in the rat

Cited by 137 publications

References 16 publications

Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats

Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats

Thermal hyperalgesia in association with the development of morphine tolerance in rats: roles of excitatory amino acid receptors and protein kinase C

Dual Ultrastructural Localization of μ-Opioid Receptors and NMDA-Type Glutamate Receptors in the Shell of the Rat Nucleus Accumbens

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