Effect of MK801 on dopamine and glutamate release after systemic L-DOPA administration in the subthalamic nucleus of intact and hemi-parkinson rats. (Poster)

Anissa El Arfani; Ben Ampe; Eduard-Mihai Bentea; Ann Massie; Sophie Sarre; Ilse Julia Smolders; Yvette Michotte

Abstract

Currently, L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for the motor symptoms in Parkinson's disease (PD). However, long term treatment with L-DOPA is associated with several motor complications such as dyskinesia. Clinical improvement of this chronic treatment is therefore needed. Lesions or high frequency stimulation of the subthalamic nucleus (STN), a glutamatergic (GLU) nucleus which has been demonstrated to be hyperactive in PD, alleviate the motor symptoms and reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA dose. It has been hypothesized that N-methyl-D-aspartate (NMDA) receptor antagonists might have similar actions by reducing the STN output and/or by altering the GLU-ergic input to the STN. However, little is known about the neurochemical changes in the STN induced by co-administration of L-DOPA with a NMDA receptor antagonist.
By means of in vivo microdialysis, the effect of dizocilpine (MK801), an NMDA receptor antagonist, on the extracellular DA and GLU levels after systemic administration of L-DOPA was investigated in the STN of intact and 6-hydroxydopamine-lesioned rats.
Extracellular DA levels in the STN increased after L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) administration in intact and DA-depleted rats. There was a tendency to a higher DA-increase in hemi-parkinson rats compared to controls. MK801 (0.1 mg/kg i.p.) did not influence the L-DOPA induced DA release in intact animals. In contrast, MK801 enhanced the L-DOPA induced DA release in hemi-parkinson rats. The extracellular GLU levels in the STN did not alter in both intact and lesioned rats after L-DOPA or L-DOPA/MK801 administration.
The present study does not support the hypothesis that MK801 alters the GLU levels in the STN. However, NMDA receptor antagonists could be used as a beneficial adjuvant treatment of PD by enhancing the therapeutic efficacy of L-DOPA.

Original language	English
Title of host publication	The Autumn Meeting 2012 of the Belgian Society of Physiology and Pharmacology
Publication status	Published - 26 Oct 2012

Keywords

Parkinson's disease
6-OHDA rat model
Subthalamic nucleus
L-DOPA
NMDA receptor antagonist
Intracerebral microdialysis
Glutamate
Dopamine

Cite this

El Arfani, Anissa ; Ampe, Ben ; Bentea, Eduard-Mihai ; Massie, Ann ; Sarre, Sophie ; Smolders, Ilse Julia ; Michotte, Yvette. / Effect of MK801 on dopamine and glutamate release after systemic L-DOPA administration in the subthalamic nucleus of intact and hemi-parkinson rats. (Poster). The Autumn Meeting 2012 of the Belgian Society of Physiology and Pharmacology. 2012.

@inbook{627f18e5cabf42c5b8ac98f3f3c282be,

title = "Effect of MK801 on dopamine and glutamate release after systemic L-DOPA administration in the subthalamic nucleus of intact and hemi-parkinson rats. (Poster)",

abstract = "Currently, L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for the motor symptoms in Parkinson's disease (PD). However, long term treatment with L-DOPA is associated with several motor complications such as dyskinesia. Clinical improvement of this chronic treatment is therefore needed. Lesions or high frequency stimulation of the subthalamic nucleus (STN), a glutamatergic (GLU) nucleus which has been demonstrated to be hyperactive in PD, alleviate the motor symptoms and reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA dose. It has been hypothesized that N-methyl-D-aspartate (NMDA) receptor antagonists might have similar actions by reducing the STN output and/or by altering the GLU-ergic input to the STN. However, little is known about the neurochemical changes in the STN induced by co-administration of L-DOPA with a NMDA receptor antagonist. By means of in vivo microdialysis, the effect of dizocilpine (MK801), an NMDA receptor antagonist, on the extracellular DA and GLU levels after systemic administration of L-DOPA was investigated in the STN of intact and 6-hydroxydopamine-lesioned rats. Extracellular DA levels in the STN increased after L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) administration in intact and DA-depleted rats. There was a tendency to a higher DA-increase in hemi-parkinson rats compared to controls. MK801 (0.1 mg/kg i.p.) did not influence the L-DOPA induced DA release in intact animals. In contrast, MK801 enhanced the L-DOPA induced DA release in hemi-parkinson rats. The extracellular GLU levels in the STN did not alter in both intact and lesioned rats after L-DOPA or L-DOPA/MK801 administration. The present study does not support the hypothesis that MK801 alters the GLU levels in the STN. However, NMDA receptor antagonists could be used as a beneficial adjuvant treatment of PD by enhancing the therapeutic efficacy of L-DOPA.",

keywords = "Parkinson's disease, 6-OHDA rat model, Subthalamic nucleus, L-DOPA, NMDA receptor antagonist, Intracerebral microdialysis, Glutamate, Dopamine",

author = "{El Arfani}, Anissa and Ben Ampe and Eduard-Mihai Bentea and Ann Massie and Sophie Sarre and Smolders, {Ilse Julia} and Yvette Michotte",

year = "2012",

month = oct,

day = "26",

language = "English",

booktitle = "The Autumn Meeting 2012 of the Belgian Society of Physiology and Pharmacology",

}

Effect of MK801 on dopamine and glutamate release after systemic L-DOPA administration in the subthalamic nucleus of intact and hemi-parkinson rats. (Poster). / El Arfani, Anissa; Ampe, Ben; Bentea, Eduard-Mihai; Massie, Ann; Sarre, Sophie; Smolders, Ilse Julia ; Michotte, Yvette.

The Autumn Meeting 2012 of the Belgian Society of Physiology and Pharmacology. 2012.

Research output: Chapter in Book/Report/Conference proceeding › Meeting abstract (Book)

TY - CHAP

T1 - Effect of MK801 on dopamine and glutamate release after systemic L-DOPA administration in the subthalamic nucleus of intact and hemi-parkinson rats. (Poster)

AU - El Arfani, Anissa

AU - Ampe, Ben

AU - Bentea, Eduard-Mihai

AU - Massie, Ann

AU - Sarre, Sophie

AU - Smolders, Ilse Julia

AU - Michotte, Yvette

PY - 2012/10/26

Y1 - 2012/10/26

N2 - Currently, L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for the motor symptoms in Parkinson's disease (PD). However, long term treatment with L-DOPA is associated with several motor complications such as dyskinesia. Clinical improvement of this chronic treatment is therefore needed. Lesions or high frequency stimulation of the subthalamic nucleus (STN), a glutamatergic (GLU) nucleus which has been demonstrated to be hyperactive in PD, alleviate the motor symptoms and reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA dose. It has been hypothesized that N-methyl-D-aspartate (NMDA) receptor antagonists might have similar actions by reducing the STN output and/or by altering the GLU-ergic input to the STN. However, little is known about the neurochemical changes in the STN induced by co-administration of L-DOPA with a NMDA receptor antagonist. By means of in vivo microdialysis, the effect of dizocilpine (MK801), an NMDA receptor antagonist, on the extracellular DA and GLU levels after systemic administration of L-DOPA was investigated in the STN of intact and 6-hydroxydopamine-lesioned rats. Extracellular DA levels in the STN increased after L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) administration in intact and DA-depleted rats. There was a tendency to a higher DA-increase in hemi-parkinson rats compared to controls. MK801 (0.1 mg/kg i.p.) did not influence the L-DOPA induced DA release in intact animals. In contrast, MK801 enhanced the L-DOPA induced DA release in hemi-parkinson rats. The extracellular GLU levels in the STN did not alter in both intact and lesioned rats after L-DOPA or L-DOPA/MK801 administration. The present study does not support the hypothesis that MK801 alters the GLU levels in the STN. However, NMDA receptor antagonists could be used as a beneficial adjuvant treatment of PD by enhancing the therapeutic efficacy of L-DOPA.

AB - Currently, L-3,4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for the motor symptoms in Parkinson's disease (PD). However, long term treatment with L-DOPA is associated with several motor complications such as dyskinesia. Clinical improvement of this chronic treatment is therefore needed. Lesions or high frequency stimulation of the subthalamic nucleus (STN), a glutamatergic (GLU) nucleus which has been demonstrated to be hyperactive in PD, alleviate the motor symptoms and reduce dyskinesia, either directly and/or by allowing the reduction of the L-DOPA dose. It has been hypothesized that N-methyl-D-aspartate (NMDA) receptor antagonists might have similar actions by reducing the STN output and/or by altering the GLU-ergic input to the STN. However, little is known about the neurochemical changes in the STN induced by co-administration of L-DOPA with a NMDA receptor antagonist. By means of in vivo microdialysis, the effect of dizocilpine (MK801), an NMDA receptor antagonist, on the extracellular DA and GLU levels after systemic administration of L-DOPA was investigated in the STN of intact and 6-hydroxydopamine-lesioned rats. Extracellular DA levels in the STN increased after L-DOPA (25 mg/kg i.p. after benserazide 10 mg/kg i.p.) administration in intact and DA-depleted rats. There was a tendency to a higher DA-increase in hemi-parkinson rats compared to controls. MK801 (0.1 mg/kg i.p.) did not influence the L-DOPA induced DA release in intact animals. In contrast, MK801 enhanced the L-DOPA induced DA release in hemi-parkinson rats. The extracellular GLU levels in the STN did not alter in both intact and lesioned rats after L-DOPA or L-DOPA/MK801 administration. The present study does not support the hypothesis that MK801 alters the GLU levels in the STN. However, NMDA receptor antagonists could be used as a beneficial adjuvant treatment of PD by enhancing the therapeutic efficacy of L-DOPA.

KW - Parkinson's disease

KW - 6-OHDA rat model

KW - Subthalamic nucleus

KW - L-DOPA

KW - NMDA receptor antagonist

KW - Intracerebral microdialysis

KW - Glutamate

KW - Dopamine

M3 - Meeting abstract (Book)

BT - The Autumn Meeting 2012 of the Belgian Society of Physiology and Pharmacology

ER -

Effect of MK801 on dopamine and glutamate release after systemic L-DOPA administration in the subthalamic nucleus of intact and hemi-parkinson rats. (Poster)

Abstract

Keywords

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