Abstract
Metabotropic glutamate receptors (mGluRs) have been recently implicated as robust therapeutic targets for Parkinson's disease (PD). Here, we explored how activation of mGluRs in globus pallidus (GP) affected the amphetamine-induced rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. The amphetamine-induced rotations were completely suppressed by the ipsilateral intrapallidal injection of the non-selective mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) and the selective group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), but not the selective group III mGluR agonist, l-2-amino-4-phosphonobutyric acid (l-AP4). The suppressive effects were detected at 2, 4, 6, 8, and 12 h after ACPD injection, but returned to the control level at 24 h. A remarkable c-fos expression was found in the lesioned side of GP, subthalamic nucleus (STN), and substantia nigra pars reticulata (SNr) of rats that received the ACPD or DHPG injection, compared to rats treated with L-AP-4 or phosphate buffer-injection. The results indicate that the blockade of amphetamine-induced rotations might be at least partially mediated by group I mGluR activation. This study advances the use of selective group I mGluRs directed toward the GP for PD treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 189-196 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 1203 |
| DOIs | |
| Publication status | Published - Apr 8 2008 |
Fingerprint
Keywords
- ACPD
- Amphetamine
- c-Fos
- DHPG
- Globus pallidus
- mGluR
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Intrapallidal metabotropic glutamate receptor activation in a rat model of Parkinson's disease : Behavioral and histological analyses. / Agari, Takashi; Yasuhara, Takao; Matsui, Toshihiro; Kuramoto, Satoshi; Kondo, Akihiko; Miyoshi, Yasuyuki; Shingo, Tetsuro; Borlongan, Cesario V.; Date, Isao.
In: Brain Research, Vol. 1203, 08.04.2008, p. 189-196.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intrapallidal metabotropic glutamate receptor activation in a rat model of Parkinson's disease
T2 - Behavioral and histological analyses
AU - Agari, Takashi
AU - Yasuhara, Takao
AU - Matsui, Toshihiro
AU - Kuramoto, Satoshi
AU - Kondo, Akihiko
AU - Miyoshi, Yasuyuki
AU - Shingo, Tetsuro
AU - Borlongan, Cesario V.
AU - Date, Isao
PY - 2008/4/8
Y1 - 2008/4/8
N2 - Metabotropic glutamate receptors (mGluRs) have been recently implicated as robust therapeutic targets for Parkinson's disease (PD). Here, we explored how activation of mGluRs in globus pallidus (GP) affected the amphetamine-induced rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. The amphetamine-induced rotations were completely suppressed by the ipsilateral intrapallidal injection of the non-selective mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) and the selective group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), but not the selective group III mGluR agonist, l-2-amino-4-phosphonobutyric acid (l-AP4). The suppressive effects were detected at 2, 4, 6, 8, and 12 h after ACPD injection, but returned to the control level at 24 h. A remarkable c-fos expression was found in the lesioned side of GP, subthalamic nucleus (STN), and substantia nigra pars reticulata (SNr) of rats that received the ACPD or DHPG injection, compared to rats treated with L-AP-4 or phosphate buffer-injection. The results indicate that the blockade of amphetamine-induced rotations might be at least partially mediated by group I mGluR activation. This study advances the use of selective group I mGluRs directed toward the GP for PD treatment.
AB - Metabotropic glutamate receptors (mGluRs) have been recently implicated as robust therapeutic targets for Parkinson's disease (PD). Here, we explored how activation of mGluRs in globus pallidus (GP) affected the amphetamine-induced rotational behavior in the unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of PD. The amphetamine-induced rotations were completely suppressed by the ipsilateral intrapallidal injection of the non-selective mGluR agonist, 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) and the selective group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), but not the selective group III mGluR agonist, l-2-amino-4-phosphonobutyric acid (l-AP4). The suppressive effects were detected at 2, 4, 6, 8, and 12 h after ACPD injection, but returned to the control level at 24 h. A remarkable c-fos expression was found in the lesioned side of GP, subthalamic nucleus (STN), and substantia nigra pars reticulata (SNr) of rats that received the ACPD or DHPG injection, compared to rats treated with L-AP-4 or phosphate buffer-injection. The results indicate that the blockade of amphetamine-induced rotations might be at least partially mediated by group I mGluR activation. This study advances the use of selective group I mGluRs directed toward the GP for PD treatment.
KW - ACPD
KW - Amphetamine
KW - c-Fos
KW - DHPG
KW - Globus pallidus
KW - mGluR
UR - http://www.scopus.com/inward/record.url?scp=40949141823&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40949141823&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2008.01.051
DO - 10.1016/j.brainres.2008.01.051
M3 - Article
C2 - 18313647
AN - SCOPUS:40949141823
VL - 1203
SP - 189
EP - 196
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -