Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats

Gossel, Matthias; Schmidt, Werner; Löscher, Wolfgang; Zaja̧czkowski, Wojciech M.; Danysz, Wojciech

doi:10.1007/bf02256627

Cited by 28 publications

(15 citation statements)

References 48 publications

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“…For example, CPP reportedly has no effect on D-2-induced stimulation of locomotor activity (Starr andStarr, 1993, 1994) whereas CPPene has synergistic effects to both D-1 and D-2 agonist-induced stimulation of locomotor activity (Svensson et al, 1992). Therefore, also the apparent inability of NBQX to modify motor responses induced by D-1 or D-2 agonists in monoamine-depleted rodents (Gossel et al, 1995) may not only be related to the suboptimal pharmacokinetic properties of the compound but also to the inherent characteristics of these acute models.…”

Section: Discussionmentioning

confidence: 92%

Differential interaction of competitive NMDA and AMPA antagonists with selective dopamine D-1 and D-2 agonists in a rat model of Parkinson's disease

Löschmann

Wüllner

Heneka

et al. 1997

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Stimulation of the dopamine (DA) D-2 and D-1 receptors results in behavioural activation (i.e., induction of contralateral rotations) in 6-hydroxydopamine (6-OHDA) substantia nigra lesioned rats. Competitive N-methyl-D-aspartate (NMDA) antagonists as well as alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonists potentiate the stimulatory responses to threshold doses of L-DOPA or the mixed dopamine D-1/D-2 agonist apomorphine in this model, indicating the potential of such combinations for the management of Parkinson's disease. Neuroanatomic and electrophysiologic data indicate a differential distribution of DA D-1 and DA D-2 receptors within motor loops of the basal ganglia. DA D-1 receptors are preferentially located on GABAergic neurones projecting to the substantia nigra compacta (SNc) and to the substantia nigra reticulata (SNr), whereas DA D-2 receptors are preferentially located on neurones that innervate the external pallidum. NMDA receptors are present in high densities within the striatum, whereas AMPA receptors are enriched in the entopeduncular nucleus/internal pallidum and the SNr. To further characterise the functional interaction between DA and glutamate receptors, we tested the competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the AMPA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f] quinoxaline (NBQX) following systemic administration in combination with the DA D-2 selective agonist quinpirole or the DAD-1 selective agonist A 68 930 (1R,3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman) in rats with chronic 6-OHDA lesions of the SNc. CPP potentiated quinpirole-induced rotations and did not affect those induced by the D-1 agonist A 68930. By contrast, NBQX had no effect on quinpirole-induced rotations, whereas synergism was seen with A 68930. These results suggest that rotations induced by combined treatment with glutamate antagonists and DA agonists are mediated by different pathways within the basal ganglia, depending on which subtype of receptor is involved. AMPA antagonists could act preferentially by activating the direct motor pathway, whereas NMDA antagonists could modulate the indirect loop.

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Section: Discussionmentioning

confidence: 92%

Differential interaction of competitive NMDA and AMPA antagonists with selective dopamine D-1 and D-2 agonists in a rat model of Parkinson's disease

Löschmann

Wüllner

Heneka

et al. 1997

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“…Danysz et al, 1994;Gossel et al, 1995;Morelti et al, 1992;Schmidt and Kretschmer, 1997). Thus, Svensson et al (1991) demonstrated a synergistic interaction of preferential DA autoreceptor antagonists with (+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine meleate ([+]MK-801) in the stimulation of locomotion.…”

Section: Introductionmentioning

confidence: 79%

“…elevations of motor activity with in combinations of MK-801 with L-Dopa (Goodwin et al, 1992), or MK-801 with dihydrexidine (Gossel et al, 1995). Neither MK-801 nor CGP 40116 restored motor activity in MPTP mice when injected with saline.…”

Section: Mptp Salinementioning

confidence: 92%

Co-administration of memantine and amantadine with sub/suprathreshold doses of L-Dopa restores motor behaviour of MPTP-treated mice

et al. 2001

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The antiparkinsonian effects of the uncompetitive NMDA antagonists, memantine, amantadine and MK-801, in combination with an acute subthreshold dose of L-Dopa (5 mg/kg) in drug-naive MPTP-treated mice or a suprathreshold dose (20 mg/kg) in L-Dopa tolerant MPTP-treated mice were investigated. In the former case, memantine (locomotion: 3 mg/kg; rearing: 1 mg/kg) and amantadine (locomotion and rearing: 10 mg/kg) injected 60 min before the subthreshold dose of L-Dopa (5 mg/kg), each induced an antiparkinsonian action in hypokinesic MPTP-treated mice that consisted of dose-specific, as opposed to dose-related, elevations of locomotion and rearing behaviour. At the same time, higher doses of memantine reduced further the rearing (10 and 30 mg/kg) and locomotor (30mg/kg) behaviour of the MPTP-treated mice. MK-801 plus L-Dopa elevated locomotion (0.1 mg/kg) but reduced rearing at the 0.3 mg/kg dose. In control, saline-treated mice, memantine (3, 10 and 30 mg/kg) and MK-801 (0.1 and 0.3 mg/kg) increased locomotor behaviour but decreased rearing behaviour, while amantadine produced no effects. Memantine increased locomotor (1 and 3 mg/kg, s.c.; 1 mg/kg dose restored activity) and rearing (0.3 and 3 mg/kg) activity in the L-Dopa tolerant MPTP-treated mice, whereas amantadine (3 and 10 mg/kg) restored both locomotor (30 mg/kg significantly increased locomotion but did not restore the activity level) and rearing (3 mg/kg only) activity. MK-801 (0.1 and 0.3 mg/kg, s.c.) also increased significantly locomotor activity of L-Dopa-tolerant MPTP mice although the antikinetic action was not reversed, thereby precluding a restorative effect of the compound. These results, demonstrating both a synergistic and a restorative effect of the NMDA antagonists in coadministration with L-Dopa, demonstrate a putative antiparkinson action by these compounds in a functional animal model that incorporates the "wearing-off" complications of L-Dopa administration in the disorder.

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“…elevations of motor activity within combinations of MK-801 with L-Dopa (Fadda and Danysz, 1988;Goodwin et al, 1992), or MK-801 with dihydrexidine (Gossel et al, 1995). Neither MK-801 nor CGP 40116 restored motor activity in MPTP mice when injected with saline.…”

Section: Restoration Effect Of Clonidine Upon Chronically L-dopa-treamentioning

confidence: 92%

Restoration and putative protection in parkinsonism

Archer

Fredriksson

2000

neurotox res

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Synergistic antiparkinsonian actions of different classes of putative therapeutic agents co-administered with a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-Dopa) (5 mg/kg) in drug-naive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice as well as the restorative actions of those compounds in suprathreshold L-Dopa-tolerant MPTP-treated mice subjected to "wearing-off" of L-Dopa efficacy were assessed in a series of experiments. The classes of compounds studied included the noncompetitive NMDA antagonists, memantine, amantadine and MK-801, the anticonvulsive and putative anticonvulsive agents, lamotrigine, FCE 26743, phenytoin, the monoamine oxidase inhibitors, L-Deprenyl, amiflamine, alpha-ethyltryptamine, clorgyline and guanfacine. In this final case, the restorative effects of clonidine and guanfacine were antagonized by the alpha(2)-adrenoceptor antagonist, yohimbine, but not the alpha(1)-adrenoceptor antagonist, prazosin. Within each class of potentially therapeutic agents a differential restorative efficacy was obtained, but the combination of different doses of apomorphine with clonidine failed to restore motor activity. Finally, the neuroprotective actions of acute and subchronic administration of the nitrone spin-trapping compound, alpha-phenyl-tert-butyl nitrone upon the spontaneous motor behaviour and striatal dopamine concentrations of MPTP-treated mice was examined.

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Effect of coadministration of glutamate receptor antagonists and dopaminergic agonists on locomotion in monoamine-depleted rats

Cited by 28 publications

References 48 publications

Differential interaction of competitive NMDA and AMPA antagonists with selective dopamine D-1 and D-2 agonists in a rat model of Parkinson's disease

Differential interaction of competitive NMDA and AMPA antagonists with selective dopamine D-1 and D-2 agonists in a rat model of Parkinson's disease

Co-administration of memantine and amantadine with sub/suprathreshold doses of L-Dopa restores motor behaviour of MPTP-treated mice

Restoration and putative protection in parkinsonism

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