Pharmacological targeting of dopamine D1 or D2 receptors evokes a rapid‐onset parkinsonian motor phenotype in mice.
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| Title: | Pharmacological targeting of dopamine D1 or D2 receptors evokes a rapid‐onset parkinsonian motor phenotype in mice. |
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| Authors: | del Agua Villa, Christian (AUTHOR), Atudorei, Mihai (AUTHOR), Siebner, Hartwig Roman (AUTHOR), Rickhag, Mattias (AUTHOR) |
| Source: | European Journal of Neuroscience. Dec2024, Vol. 60 Issue 12, p7006-7024. 19p. |
| Subjects: | Dopamine receptors, Parkinson's disease, Parallel electric circuits, Dopamine antagonists, Induction motors |
| Abstract: | Dopaminergic nigrostriatal denervation in Parkinson's disease (PD) disrupts the functional balance between striatal projecting neurons, leading to aberrant activity in the cortico‐basal ganglia circuit and characteristic motor symptoms. While genetic and toxin‐based animal models are commonly used to mimic PD pathology and behaviour, they have limitations when combined with circuit manipulation tools. This highlights the need for complementary approaches, particularly when combined with viral‐based circuit targeting of specific neuronal subpopulations involved in PD circuit dysfunction. Here, we pursue a pharmacological approach targeting dopamine D1 or D2 receptors to induce dopamine deprivation and to replicate key motor symptoms in PD. We demonstrate a clear dose‐dependent induction of parkinsonian motor behaviour by both a dopamine D1 receptor antagonist (SCH23390) and a D2 receptor antagonist (haloperidol). The motor phenotype is evaluated by considering relevant motor metrics in an open‐field maze platform. The proposed parkinsonian pharmacological model constitutes an acute, flexible approach, which allows parallel brain circuit manipulations. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| Abstract: | Dopaminergic nigrostriatal denervation in Parkinson's disease (PD) disrupts the functional balance between striatal projecting neurons, leading to aberrant activity in the cortico‐basal ganglia circuit and characteristic motor symptoms. While genetic and toxin‐based animal models are commonly used to mimic PD pathology and behaviour, they have limitations when combined with circuit manipulation tools. This highlights the need for complementary approaches, particularly when combined with viral‐based circuit targeting of specific neuronal subpopulations involved in PD circuit dysfunction. Here, we pursue a pharmacological approach targeting dopamine D1 or D2 receptors to induce dopamine deprivation and to replicate key motor symptoms in PD. We demonstrate a clear dose‐dependent induction of parkinsonian motor behaviour by both a dopamine D1 receptor antagonist (SCH23390) and a D2 receptor antagonist (haloperidol). The motor phenotype is evaluated by considering relevant motor metrics in an open‐field maze platform. The proposed parkinsonian pharmacological model constitutes an acute, flexible approach, which allows parallel brain circuit manipulations. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 0953816X |
| DOI: | 10.1111/ejn.16622 |
