Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease
Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Wei, Shi-Zhuang [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021transfer abstract |
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| Schlagwörter: |
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| Umfang: |
10 |
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| Übergeordnetes Werk: |
Enthalten in: Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons - Orts-Del’Immagine, Adeline ELSEVIER, 2017, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:177 ; year:2021 ; pages:363-372 ; extent:10 |
| Links: |
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| DOI / URN: |
10.1016/j.brainresbull.2021.10.015 |
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| 520 | |a Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. | ||
| 520 | |a Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. | ||
| 650 | 7 | |a Depression-like behavior |2 Elsevier | |
| 650 | 7 | |a Dopamine D2 receptor |2 Elsevier | |
| 650 | 7 | |a Dopamine D3 receptor |2 Elsevier | |
| 650 | 7 | |a Parkinson’s disease |2 Elsevier | |
| 650 | 7 | |a Pramipexole |2 Elsevier | |
| 700 | 1 | |a Yao, Xiao-Yu |4 oth | |
| 700 | 1 | |a Wang, Chen-Tao |4 oth | |
| 700 | 1 | |a Dong, An-Qi |4 oth | |
| 700 | 1 | |a Li, Dan |4 oth | |
| 700 | 1 | |a Zhang, Yu-Ting |4 oth | |
| 700 | 1 | |a Ren, Chao |4 oth | |
| 700 | 1 | |a Zhang, Jin-Bao |4 oth | |
| 700 | 1 | |a Mao, Cheng-Jie |4 oth | |
| 700 | 1 | |a Wang, Fen |4 oth | |
| 700 | 1 | |a Liu, Chun-Feng |4 oth | |
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10.1016/j.brainresbull.2021.10.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001983.pica (DE-627)ELV055862578 (ELSEVIER)S0361-9230(21)00307-5 DE-627 ger DE-627 rakwb eng 610 VZ 630 640 VZ 58.34 bkl Wei, Shi-Zhuang verfasserin aut Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease 2021transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression-like behavior Elsevier Dopamine D2 receptor Elsevier Dopamine D3 receptor Elsevier Parkinson’s disease Elsevier Pramipexole Elsevier Yao, Xiao-Yu oth Wang, Chen-Tao oth Dong, An-Qi oth Li, Dan oth Zhang, Yu-Ting oth Ren, Chao oth Zhang, Jin-Bao oth Mao, Cheng-Jie oth Wang, Fen oth Liu, Chun-Feng oth Enthalten in Elsevier Science Orts-Del’Immagine, Adeline ELSEVIER Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons 2017 Amsterdam [u.a.] (DE-627)ELV020160690 volume:177 year:2021 pages:363-372 extent:10 https://doi.org/10.1016/j.brainresbull.2021.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_23 GBV_ILN_60 58.34 Lebensmitteltechnologie VZ AR 177 2021 363-372 10 |
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10.1016/j.brainresbull.2021.10.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001983.pica (DE-627)ELV055862578 (ELSEVIER)S0361-9230(21)00307-5 DE-627 ger DE-627 rakwb eng 610 VZ 630 640 VZ 58.34 bkl Wei, Shi-Zhuang verfasserin aut Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease 2021transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression-like behavior Elsevier Dopamine D2 receptor Elsevier Dopamine D3 receptor Elsevier Parkinson’s disease Elsevier Pramipexole Elsevier Yao, Xiao-Yu oth Wang, Chen-Tao oth Dong, An-Qi oth Li, Dan oth Zhang, Yu-Ting oth Ren, Chao oth Zhang, Jin-Bao oth Mao, Cheng-Jie oth Wang, Fen oth Liu, Chun-Feng oth Enthalten in Elsevier Science Orts-Del’Immagine, Adeline ELSEVIER Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons 2017 Amsterdam [u.a.] (DE-627)ELV020160690 volume:177 year:2021 pages:363-372 extent:10 https://doi.org/10.1016/j.brainresbull.2021.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_23 GBV_ILN_60 58.34 Lebensmitteltechnologie VZ AR 177 2021 363-372 10 |
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10.1016/j.brainresbull.2021.10.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001983.pica (DE-627)ELV055862578 (ELSEVIER)S0361-9230(21)00307-5 DE-627 ger DE-627 rakwb eng 610 VZ 630 640 VZ 58.34 bkl Wei, Shi-Zhuang verfasserin aut Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease 2021transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression-like behavior Elsevier Dopamine D2 receptor Elsevier Dopamine D3 receptor Elsevier Parkinson’s disease Elsevier Pramipexole Elsevier Yao, Xiao-Yu oth Wang, Chen-Tao oth Dong, An-Qi oth Li, Dan oth Zhang, Yu-Ting oth Ren, Chao oth Zhang, Jin-Bao oth Mao, Cheng-Jie oth Wang, Fen oth Liu, Chun-Feng oth Enthalten in Elsevier Science Orts-Del’Immagine, Adeline ELSEVIER Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons 2017 Amsterdam [u.a.] (DE-627)ELV020160690 volume:177 year:2021 pages:363-372 extent:10 https://doi.org/10.1016/j.brainresbull.2021.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_23 GBV_ILN_60 58.34 Lebensmitteltechnologie VZ AR 177 2021 363-372 10 |
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10.1016/j.brainresbull.2021.10.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001983.pica (DE-627)ELV055862578 (ELSEVIER)S0361-9230(21)00307-5 DE-627 ger DE-627 rakwb eng 610 VZ 630 640 VZ 58.34 bkl Wei, Shi-Zhuang verfasserin aut Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease 2021transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression-like behavior Elsevier Dopamine D2 receptor Elsevier Dopamine D3 receptor Elsevier Parkinson’s disease Elsevier Pramipexole Elsevier Yao, Xiao-Yu oth Wang, Chen-Tao oth Dong, An-Qi oth Li, Dan oth Zhang, Yu-Ting oth Ren, Chao oth Zhang, Jin-Bao oth Mao, Cheng-Jie oth Wang, Fen oth Liu, Chun-Feng oth Enthalten in Elsevier Science Orts-Del’Immagine, Adeline ELSEVIER Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons 2017 Amsterdam [u.a.] (DE-627)ELV020160690 volume:177 year:2021 pages:363-372 extent:10 https://doi.org/10.1016/j.brainresbull.2021.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_23 GBV_ILN_60 58.34 Lebensmitteltechnologie VZ AR 177 2021 363-372 10 |
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10.1016/j.brainresbull.2021.10.015 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001983.pica (DE-627)ELV055862578 (ELSEVIER)S0361-9230(21)00307-5 DE-627 ger DE-627 rakwb eng 610 VZ 630 640 VZ 58.34 bkl Wei, Shi-Zhuang verfasserin aut Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease 2021transfer abstract 10 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. Depression-like behavior Elsevier Dopamine D2 receptor Elsevier Dopamine D3 receptor Elsevier Parkinson’s disease Elsevier Pramipexole Elsevier Yao, Xiao-Yu oth Wang, Chen-Tao oth Dong, An-Qi oth Li, Dan oth Zhang, Yu-Ting oth Ren, Chao oth Zhang, Jin-Bao oth Mao, Cheng-Jie oth Wang, Fen oth Liu, Chun-Feng oth Enthalten in Elsevier Science Orts-Del’Immagine, Adeline ELSEVIER Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons 2017 Amsterdam [u.a.] (DE-627)ELV020160690 volume:177 year:2021 pages:363-372 extent:10 https://doi.org/10.1016/j.brainresbull.2021.10.015 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_23 GBV_ILN_60 58.34 Lebensmitteltechnologie VZ AR 177 2021 363-372 10 |
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Enthalten in Postnatal maturation of mouse medullo-spinal cerebrospinal fluid-contacting neurons Amsterdam [u.a.] volume:177 year:2021 pages:363-372 extent:10 |
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Pramipexole regulates depression-like behavior via dopamine D3 receptor in a mouse model of Parkinson’s disease |
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Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. |
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Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. |
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Depression is one of the strongest predictors of quality of life in patients with Parkinson’s disease (PD). Despite the high prevalence of depression, there is no clear guidance for its treatment in PD because the evidence for the efficacy of most antidepressants remains insufficient. Pramipexole, a dopamine agonist, is one of the few drugs that has proven to be clinically useful. However, the underlying mechanisms of antidepressive effects of pramipexole are still unknown. A 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model, dopamine D2 receptor (DRD2) and D3 receptor (DRD3) knockout mice were used in our study. Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. Our findings highlight the need to develop novel dopamine agonists specifically targeting DRD3 for the treatment of depression in PD in the future. |
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Compared with other dopamine D2-like receptor agonists and madopar, pramipexole improved depression-like behavior and alleviate bradykinesia in an MPTP-induced mouse model of PD. Pramipexole significantly improved depression-like behavior in DRD2−/− mice but not in DRD3−/− mice. These results demonstrate that the antidepressive effect of pramipexole is mediated by DRD3 but not DRD2. 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