Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat

Marek, Przemysław; Ben‐Eliyahu, Shamgar; Gold, Michael S.; Liebeskind, John C.

doi:10.1016/0006-8993(91)90576-h

Cited by 271 publications

(114 citation statements)

References 18 publications

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“…Since MK801 prevents morphine tolerance and dependence in rats (5,6), the striatum and NA would be among the many candidate regions for mediating tolerance and dependence to opiates.…”

Section: Discussionmentioning

confidence: 99%

“…If there were common DA-mediated mechanisms of addiction for opiates, cocaine, and amphetamine (1,4), these drugs should induce IEGs in similar brain regions. Moreover, since DA and its receptors are implicated in opiate and cocaine addiction (1)(2)(3)(4), and N-methyl-D-aspartate (NMDA) receptors are implicated in opiate dependence and tolerance (5,6), DA and NMDA receptor antagonists might block morphine induction of IEGs in brain regions that mediate behaviors that contribute to opiate abuse.…”

mentioning

confidence: 99%

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Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Liu

Nickolenko

Sharp

1994

Proc. Natl. Acad. Sci. U.S.A.

168

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Morphine induced the c-fos and junB immediate early genes in neurons of the medial and ventral striatn and nucleus accumbens. Induction of c-fos and junB mRNA and Fos protein was blocked by naloxone, the D1 dopamine (DA) receptor antagonists SCH23390 and SCH39166, and the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK801. SCH23390 attenuated morphine induction of AP-1 binding in striatum, suggesting that c-fos andjunB contribute to AP-1 binding. SCH23390 and MK801 did not block morphine induction of c-fos and junB in septum. Since the morphine induction of c-fos and junE in striatum and nucleus accumbens (NA) was similar to that observed with cocaine and amphetamine, these data support current concepts that limbic striatum and NA are among the brain regions that mediate drug abuse. Furthermore, since DA and NMDA receptors may mediate opiate reward and opiate induction of c-fos andjunE, the DA/NMDA regulation of c-fos and junB and their target genes may produce long-term changes in the striatal and NA circuits that contribute to opiate drug abuse.

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“…Since MK801 prevents morphine tolerance and dependence in rats (5,6), the striatum and NA would be among the many candidate regions for mediating tolerance and dependence to opiates.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Liu

Nickolenko

Sharp

1994

Proc. Natl. Acad. Sci. U.S.A.

168

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“…As early as 1991, Marek et al (1991) and Trujillo and Akil Presented are mean 7 SEM times spent in morphine-associated arm of the apparatus before (pre-test) and after (post-test) conditioning as well as the mean difference between these times for each group (preference (%)) expressed as an average relative % change between pretest (100%) and post-test for each mouse tested. Mice were conditioned to the effects of morphine (10 mg/kg) and treated with 2-PMPA (100 mg/kg) or memantine (7.5 mg/kg) during conditionings or before the post-test to investigate the effects on acquisition and expression, respectively.…”

Section: Effects Of Gcp II Inhibition On Morphine Tolerancementioning

confidence: 99%

“…Glutamate, a major excitatory neurotransmitter in the brain, stimulates both ionotropic and metabotropic glutamate receptors (Monaghan et al, 1989;Conn and Pin, 1997). Antagonists of the ionotropic N-methyl-d-aspartate (NMDA) receptor complex, including memantine, the low affinity, and highly voltage-dependent clinically available NMDA receptor antagonist, inhibit the development of morphine tolerance (Trujillo and Akil, 1991;Marek et al, 1991;Popik et al, 2000a) and reverse pre-existing tolerance so that opiatetolerant animals treated with NMDA receptor antagonists become sensitive to doses of morphine that previously did not evoke antinociception (Tiseo and Inturrisi, 1993;Popik et al, 2000a). Antagonists of this receptor complex also attenuate the development (Trujillo and Akil, 1991), expression (Cappendijk et al, 1993), and maintenance of the continuing morphine dependence.…”

Section: Introductionmentioning

confidence: 99%

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Neuropsychopharmacol

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Inhibition of glutamate carboxypeptidase II (GCP II; NAALADase) produces a variety of effects on glutamatergic neurotransmission. The aim of this study was to investigate effects of GCP II inhibition with the selective inhibitor, 2-PMPA, on: (a) development of tolerance to the antinociceptive effects, (b) withdrawal, and (c) conditioned reward produced by morphine in C57/Bl mice. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily (b.i.d.) administration of 2-PMPA and 10 mg/kg of morphine. Opioid withdrawal was measured 3 days after twice daily morphine (30 or 10 mg/kg) administration, followed by naloxone challenge. Conditioned morphine reward was investigated using conditioned place preference with a single morphine dose (10 mg/kg). High doses of 2-PMPA inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist, memantine) while not affecting the severity of withdrawal. A high dose of 2-PMPA (100 mg/kg) also significantly potentiated morphine withdrawal, but inhibited both acquisition and expression of morphine-induced conditioned place preference. Memantine inhibited the intensity of morphine withdrawal as well as acquisition and expression of morphine-induced conditioned place preference. In addition, 2-PMPA did not affect learning or memory retrieval in a simple two-trial test, nor did it produce withdrawal symptoms in morphinedependent, placebo-challenged mice. Results suggest involvement of GCP II (NAALADase) in phenomena related to opioid addiction.

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“…Recently, NMDA receptors have been recognized as a critical factor underlying tolerance to various drugs of abuse. Trujillo and Akil (1991) and Marek et al (1991) were the first to report that intraventricular infusion of MK-801 (dizocilpine maleate), a selective noncompetitive NMDA receptor antagonist, could strongly attenuate the morphine withdrawal syndrome, a finding subsequently confirmed by others (Tiseo et al, 1994;Elliott et al, 1995).Numerous studies established that NMDA receptors, formed by the association of two or more subunits, have multiple binding sites for various agents such as endogenous agonists, competitive antagonists, and Mg 2ϩ , Zn 2ϩ , or polyamines. To date, five NMDA receptors subunits (NR1, NR2A-D) have been identified.…”

mentioning

confidence: 99%

Chronic Morphine Treatment AltersN-Methyl-d-aspartate Receptors in Freshly Isolated Neurons from Nucleus Accumbens

Martin

Guadaño-Ferraz²,

Morte³

et al. 2004

J Pharmacol Exp Ther

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Although there is now evidence of a role for N-methyl-D-aspartate (NMDA) receptors in nucleus accumbens (NAcc) neurons in the effects of chronic opiate treatment, the cellular and molecular mechanisms underlying this phenomenon are still unclear. Therefore, we studied the effects of chronic morphine on the pharmacological and biophysical properties of NMDA receptors in freshly isolated medium spiny neurons from NAcc. We found that chronic morphine treatment did not alter the affinity for NMDA receptor agonists such as glutamate, homoquinolinic acid, and NMDA, but decreased the affinity of glycine, the allosteric NMDA receptor coagonist, from 2.24 Ϯ 0.15 M to 5.1 Ϯ 1.45 M. Chronic morphine treatment also altered the affinity of two noncompetitive NMDA receptor antagonists, 7-chloro-kynurenic acid and ifenprodil. However, morphine had no effect on a third antagonist, D-(Ϫ)-2-amino-5-phosphonopentanoic acid. Single-exponential fits of desensitized NMDA current tails gave tau values ranging from 0.5 to 4 s in neurons from both control and morphine-treated rats. However, a shift to the left of the distribution of tau values after morphine treatment revealed that NMDA current desensitization rate was accelerated in a majority of NAcc neurons. Taken together with our recent molecular studies, our data are consistent with a shift away from NMDA receptor subunit (NR) NR2B and 2C function toward increased NR2A subunit expression or function after chronic morphine, a process that could alter excitability and integrative properties and may represent a neuroadaptation of NAcc medium spiny neurons underlying morphine dependence.During the past decade the nucleus accumbens, an interface between limbic regions and the extrapyramidal motor system, has emerged as a key structure mediating the acute and chronic behavioral effects of drugs of abuse (Koob et al., 1992). Although behavioral studies conclusively demonstrated a key role for NAcc in opiate self-administration, relatively little is known about the cellular and molecular mechanisms responsible for acute opiate effects, and even more remains to be understood about chronic effects. Recently, NMDA receptors have been recognized as a critical factor underlying tolerance to various drugs of abuse. Trujillo and Akil (1991) and Marek et al. (1991) were the first to report that intraventricular infusion of MK-801 (dizocilpine maleate), a selective noncompetitive NMDA receptor antagonist, could strongly attenuate the morphine withdrawal syndrome, a finding subsequently confirmed by others (Tiseo et al., 1994;Elliott et al., 1995).Numerous studies established that NMDA receptors, formed by the association of two or more subunits, have multiple binding sites for various agents such as endogenous agonists, competitive antagonists, and Mg 2ϩ , Zn 2ϩ , or polyamines. To date, five NMDA receptors subunits (NR1, NR2A-D) have been identified. It is believed that, in native NMDA receptors, these subunits are assembled in various combinations to create heteromultimeric receptors. In...

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Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat

Cited by 271 publications

References 18 publications

Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Morphine induces c-fos and junB in striatum and nucleus accumbens via D1 and N-methyl-D-aspartate receptors.

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Chronic Morphine Treatment AltersN-Methyl-d-aspartate Receptors in Freshly Isolated Neurons from Nucleus Accumbens

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