Dizocilpine(MK-801) Blocks Tolerance to the Analgesic but Not to the Hyperthermic Effect of Morphine in the Rat

Bhargava, Hemendra N.; Matwyshyn, George A.

doi:10.1159/000139117

Cited by 54 publications

(27 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…First, both the present as well as earlier work (Lutfy et al 1993;Elliott et al 1994a;Bilsky et al 1996;Gonzalez et al 1997;Belozertseva and Bespalov 1998;Lutfy et al 1995) demonstrate similar, inhibitory effects on morphine tolerance produced by a number of structurally dissimilar NMDA receptor antagonists. In addition, the findings of Bhargava and Matwyshyn (1993) demonstrating that (+)MK-801 inhibits the tolerance to the antinociceptive but not to the hyperthermic effect of morphine, suggest that pharmacokinetic interaction between an NMDA receptor antagonist and morphine is unlikely.…”

Section: Discussionmentioning

confidence: 99%

Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice

Popik

Kozela

Danysz

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

View full text Add to dashboard Cite

The tail-flick test was used to investigate the effects of chronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonists, dextromethorphan, memantine and MRZ 2/579, on the development and reversal of morphine tolerance in mice in three separate experiments. Experiment 1 investigated the effects of NMDA receptor antagonists on the development of tolerance. Morphine (10 mg/kg for 6 days, twice daily) produced a 5.9-fold rightward shift of the cumulative dose-response curves. Co-administration of dextromethorphan, memantine or MRZ 2/579 between tests 1 and 2 dose-dependently (5-10 mg/kg) inhibited the development of morphine tolerance. In experiment 2, in which the effects on the reversal were investigated, morphine-tolerant mice were treated b.i.d. for an additional 6 days (between tests 2 and 3) with vehicle+vehicle, NMDA receptor antagonist+vehicle, vehicle+morphine or NMDA receptor antagonist+morphine. Morphine-tolerant mice treated with vehicle+vehicle remained morphine tolerant, whereas this residual morphine tolerance was inhibited by administration of all three NMDA antagonists (each 10 mg/kg). Morphine-tolerant mice receiving vehicle+morphine injections demonstrated an unchanged degree of antinociceptive tolerance. In these mice, the co-administration of memantine and MRZ 2/579, but not dextromethorphan, resulted in the reversal of morphine tolerance. In experiment 3, memantine and MRZ 2/579 (10 mg/kg) inhibited the acute antinociceptive effect of morphine, but dextromethorphan did not. These data indicate that low-affinity, clinically available and/or therapeutically promising NMDA receptor antagonists may be used to inhibit ongoing morphine tolerance.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice

Popik

Kozela

Danysz

2000

Naunyn-Schmiedeberg's Archives of Pharmacology

View full text Add to dashboard Cite

show abstract

“…For instance, NMDA receptors have been implicated in the pain process [1], analgesic actions of opioid agents [2] in the development of tolerance to and physical dependence on opiates [3][4][5] and in the opioid withdrawal syndrome [6,7], Additionally, chronic administration of mor phine causes down-regulation of brain NMDA receptors [8,9], Most of these studies have used mice and rats and some differences have been noted in the actions of NMDA receptor antagonists on the acute and chronic actions of opiates. Thus, whereas the noncom petitive NMDA receptor antagonist, MK-801, was shown not to affect morphine anal gesia in the rat [4,5], it was effective in antag-onizing the analgesic response to morphine in mice [2].…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Synthase Activity in Brain Regions and Spinal Cord of Mice and Rats: Kinetic Analysis

Barjavel

Bhargava

1995

Pharmacology

Self Cite

View full text Add to dashboard Cite

Nitric oxide synthase (NOS) activity was determined by the rate of conversion of [³H]arginine to [³H]citrulline in brain regions (midbrain, hypothalamus, cerebellum, hippocampus, corpus striatum, cortex, pons-medulla and amygdala) and spinal cord of male Swiss Webster mice and male Sprague-Dawley rats. In mice, high activity of NOS was found in cerebellum, hypothalamus and midbrain; intermediate activity in pons-medulla, hippocampus, amygdala, corpus striatum and cortex; and low activity in the spinal cord. In rat, highest activity of NOS was observed in cerebellum followed in decreasing order by midbrain, hypothalamus, cortex, striatum, pons-medulla, hippocampus and spinal cord. In all tissues, NOS activity was higher in rat than in mouse. Analysis of the Eadie-Hofstee plot indicated that the V_max and K_m values of the enzyme in cortex and cerebellum of rats were higher than in mouse tissues. These studies show differential distribution of NOS activity in mouse and rat brain regions and spinal cord and higher activity of NOS in rat brain regions and spinal cord compared to mouse tissues.

show abstract

“…Previous studies from this laboratory have provided evidence for the dissociation of tolerance to the analgesic and hpyothermic actions of morphine in the mouse using thyro tropin-releasing hormone [28]. Similarly, tol erance to the analgesic action of morphine can be blocked by MK-801, an inhibitor of NMDA receptor, but the tolerance to the hypothermic action of morphine cannot be blocked by MK-801 [ 10], indicating that the two processes may involve distinct mechanisms.…”

Section: Discussionmentioning

confidence: 97%

Nitric Oxide Synthase Inhibition Blocks Tolerance to the Analgesic Action of k-Opiate Receptor Agonist in the Rat

Bhargava

1994

Pharmacology

Self Cite

View full text Add to dashboard Cite

The effect of N^G-monomethyl-L-arginine (NMMA), an inhibitor of nitric oxide synthase, on the development of tolerance to the analgesic and hypothermic actions of U-50,488H, a highly selective ĸ-opiate agonist, was determined in the rat. Male Sprague-Dawley rats were rendered tolerant to the pharmacological actions of U-50,488H by twice daily intraperitoneal injections of the drug (25 mg/kg) for 4 days. To determine the effect of NMMA on tolerance to U-50,488H, NMMA was administered 10 min prior to each injection of U-50,488H. Multiple injections of U-50,488H resulted in the development of tolerance to its analgesic and hypothermic actions. NMMA (2, 4 and 8 mg/kg) inhibited the development of tolerance to the analgesic but not to the hypothermic action of U-50,488H. Multiple injections of U-50,488H resulted in a slower gain in body weight which was not modified by treatment with NMMA. The results indicate that inhibition of nitric oxide synthase can selectively block the tolerance to its analgesic action in the rat.

show abstract

Dizocilpine(MK-801) Blocks Tolerance to the Analgesic but Not to the Hyperthermic Effect of Morphine in the Rat

Cited by 54 publications

References 10 publications

Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice

Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice

Nitric Oxide Synthase Activity in Brain Regions and Spinal Cord of Mice and Rats: Kinetic Analysis

Nitric Oxide Synthase Inhibition Blocks Tolerance to the Analgesic Action of k-Opiate Receptor Agonist in the Rat

Contact Info

Product

Resources

About