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The 5-HT(2A) Receptor Antagonist M100907 Produces Antiparkinsonian Effects and Decreases Striatal Glutamate.

Ansah TA, Ferguson MC, Nayyar T - Front Syst Neurosci (2011)

Bottom Line: 5-HT plays a regulatory role in voluntary movements of the basal ganglia and has a major impact on disorders of the basal ganglia such as Parkinson's disease (PD).We hypothesized that 5-HT(2A) receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum.In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Pharmacology, Meharry Medical College Nashville, TN, USA.

ABSTRACT
5-HT plays a regulatory role in voluntary movements of the basal ganglia and has a major impact on disorders of the basal ganglia such as Parkinson's disease (PD). Clinical studies have suggested that 5-HT(2) receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT(2A) receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT(2A) receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT(2A) receptors may represent a novel therapeutic target for the motor symptoms of PD.

No MeSH data available.


Related in: MedlinePlus

Dopamine concentrations in subcortical regions of saline and MPTP-treated mice. Dopamine concentrations were determined 3 weeks after the last MPTP injection. In addition to changes in the striatal complex, a significant decrease in dopamine in the substantia nigra was seen (n = 10/group). Abbreviations: CER, cerebellar cortex; NAc, nucleus accumbens; SN, substantia nigra; STR, striatum. Data are expressed as percent of saline-injected control mice. Dopamine concentrations (mean ng/mg protein ± SEM) in control mice: STR: 144.7 ± 9.3; NAc: 14.1 ± 0.54; SN: 6.8 ± 0.5; CER: 0.17 ± 0.05. *p < 0.05, **p < 0.01; relative to saline-injected controls.
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Figure 1: Dopamine concentrations in subcortical regions of saline and MPTP-treated mice. Dopamine concentrations were determined 3 weeks after the last MPTP injection. In addition to changes in the striatal complex, a significant decrease in dopamine in the substantia nigra was seen (n = 10/group). Abbreviations: CER, cerebellar cortex; NAc, nucleus accumbens; SN, substantia nigra; STR, striatum. Data are expressed as percent of saline-injected control mice. Dopamine concentrations (mean ng/mg protein ± SEM) in control mice: STR: 144.7 ± 9.3; NAc: 14.1 ± 0.54; SN: 6.8 ± 0.5; CER: 0.17 ± 0.05. *p < 0.05, **p < 0.01; relative to saline-injected controls.

Mentions: To evaluate the extent of dopaminergic lesion, the levels of DA in the striatum, substantia nigra, nucleus accumbens and cerebellum were measured by HPLC. MPTP treatment had significant main effect on DA in subcortical regions [F(7,107) = 4.542; p < 0.001; Figure 1]. Post hoc analysis revealed that DA was significantly decreased in the striatum (p < 0.01), substantia nigra and nucleus accumbens (p < 0.05) but not in the cerebellum. The 5-HT content in these brain regions of MPTP-treated mice remained generally unchanged except for a small but insignificant decrease in the substantia nigra (data not shown).


The 5-HT(2A) Receptor Antagonist M100907 Produces Antiparkinsonian Effects and Decreases Striatal Glutamate.

Ansah TA, Ferguson MC, Nayyar T - Front Syst Neurosci (2011)

Dopamine concentrations in subcortical regions of saline and MPTP-treated mice. Dopamine concentrations were determined 3 weeks after the last MPTP injection. In addition to changes in the striatal complex, a significant decrease in dopamine in the substantia nigra was seen (n = 10/group). Abbreviations: CER, cerebellar cortex; NAc, nucleus accumbens; SN, substantia nigra; STR, striatum. Data are expressed as percent of saline-injected control mice. Dopamine concentrations (mean ng/mg protein ± SEM) in control mice: STR: 144.7 ± 9.3; NAc: 14.1 ± 0.54; SN: 6.8 ± 0.5; CER: 0.17 ± 0.05. *p < 0.05, **p < 0.01; relative to saline-injected controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117200&req=5

Figure 1: Dopamine concentrations in subcortical regions of saline and MPTP-treated mice. Dopamine concentrations were determined 3 weeks after the last MPTP injection. In addition to changes in the striatal complex, a significant decrease in dopamine in the substantia nigra was seen (n = 10/group). Abbreviations: CER, cerebellar cortex; NAc, nucleus accumbens; SN, substantia nigra; STR, striatum. Data are expressed as percent of saline-injected control mice. Dopamine concentrations (mean ng/mg protein ± SEM) in control mice: STR: 144.7 ± 9.3; NAc: 14.1 ± 0.54; SN: 6.8 ± 0.5; CER: 0.17 ± 0.05. *p < 0.05, **p < 0.01; relative to saline-injected controls.
Mentions: To evaluate the extent of dopaminergic lesion, the levels of DA in the striatum, substantia nigra, nucleus accumbens and cerebellum were measured by HPLC. MPTP treatment had significant main effect on DA in subcortical regions [F(7,107) = 4.542; p < 0.001; Figure 1]. Post hoc analysis revealed that DA was significantly decreased in the striatum (p < 0.01), substantia nigra and nucleus accumbens (p < 0.05) but not in the cerebellum. The 5-HT content in these brain regions of MPTP-treated mice remained generally unchanged except for a small but insignificant decrease in the substantia nigra (data not shown).

Bottom Line: 5-HT plays a regulatory role in voluntary movements of the basal ganglia and has a major impact on disorders of the basal ganglia such as Parkinson's disease (PD).We hypothesized that 5-HT(2A) receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum.In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Pharmacology, Meharry Medical College Nashville, TN, USA.

ABSTRACT
5-HT plays a regulatory role in voluntary movements of the basal ganglia and has a major impact on disorders of the basal ganglia such as Parkinson's disease (PD). Clinical studies have suggested that 5-HT(2) receptor antagonists may be useful in the treatment of the motor symptoms of PD. We hypothesized that 5-HT(2A) receptor antagonists may restore motor function by regulating glutamatergic activity in the striatum. Mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exhibited decreased performance on the beam-walking apparatus. Peripheral administration of the 5-HT(2A) receptor antagonist M100907 improved performance of MPTP-treated mice on the beam-walking apparatus. In vivo microdialysis revealed an increase in striatal extracellular glutamate in MPTP-treated mice and local perfusion of M100907 into the dorsal striatum significantly decreased extracellular glutamate levels in saline and MPTP-treated mice. Our studies suggest that blockade of 5-HT(2A) receptors may represent a novel therapeutic target for the motor symptoms of PD.

No MeSH data available.


Related in: MedlinePlus