Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats
Background: Motor impairments in Parkinson's disease (PD) are associated with alterations in the prepulse inhibition (PPI) of the acoustic startle response (ASR) and reversal learning (RL) from the early stages of the disease. In this context, animal models enable the exploration of the dynamic...
- Autores:
-
Lievano Parra, Diego Javier
- Tipo de recurso:
- Doctoral thesis
- Fecha de publicación:
- 2023
- Institución:
- Universidad de los Andes
- Repositorio:
- Séneca: repositorio Uniandes
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.uniandes.edu.co:1992/73645
- Acceso en línea:
- https://hdl.handle.net/1992/73645
- Palabra clave:
- Parkinson's disease
Reversal learning
Prepulse inhibition
6-OHDA
Rat
Psicología
- Rights
- openAccess
- License
- Attribution-NonCommercial-NoDerivatives 4.0 International
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| dc.title.eng.fl_str_mv |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| title |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| spellingShingle |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats Parkinson's disease Reversal learning Prepulse inhibition 6-OHDA Rat Psicología |
| title_short |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| title_full |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| title_fullStr |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| title_full_unstemmed |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| title_sort |
Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar rats |
| dc.creator.fl_str_mv |
Lievano Parra, Diego Javier |
| dc.contributor.advisor.none.fl_str_mv |
Cárdenas Parra, Luis Fernando |
| dc.contributor.author.none.fl_str_mv |
Lievano Parra, Diego Javier |
| dc.contributor.jury.none.fl_str_mv |
Báez Buitrago, Sandra Jimena Sabogal, Angelica |
| dc.contributor.researchgroup.none.fl_str_mv |
Facultad de Ciencias Sociales::Neurociencia y Comportamiento |
| dc.subject.keyword.eng.fl_str_mv |
Parkinson's disease |
| topic |
Parkinson's disease Reversal learning Prepulse inhibition 6-OHDA Rat Psicología |
| dc.subject.keyword.none.fl_str_mv |
Reversal learning Prepulse inhibition 6-OHDA Rat |
| dc.subject.themes.spa.fl_str_mv |
Psicología |
| description |
Background: Motor impairments in Parkinson's disease (PD) are associated with alterations in the prepulse inhibition (PPI) of the acoustic startle response (ASR) and reversal learning (RL) from the early stages of the disease. In this context, animal models enable the exploration of the dynamics of non-motor manifestations associated to dopaminergic depletion in a time-dependent manner. Method: 103 adult male and female Wistar rats received unilateral injections of 6-OHDA or saline into the Substantia Nigra Compacta (SNc). Motor skills and the PPI were assessed before and after surgery. Subsequently, three groups were formed to evaluate action-based RL (AB) and stimulus-based RL (SB). Results: The apomorphine test at 2 weeks confirmed the establishment of dopaminergic depletion. Motor coordination was affected in the lesioned groups, with higher number of grip errors and reduced running speed in lesioned males 6 weeks after surgery. The percentage PPI decreased in lesioned females at 4 weeks but increased in lesioned males 6 weeks after lesioning. Finally, the 6-OHDA lesion did not affect initial discrimination or reversal in the AB task, although a treatment facilitation effect was observed in the reversal of SB task. Additionally, sex-dependent differences were observed in performance. Males showed more perseverative behavior and a higher percentage of the win-stay strategy, while females exhibited slower response latencies for both correct and incorrect responses, displaying a higher percentage of the lose-shift strategy. Conclusion: The results show that subthreshold dopamine depletions in the SNc in the unilateral rodent model of 6-OHDA caused sex-differential effects on PPI and RL with more noticeable motor impairments in males after six weeks after surgery. Further characterization of how PPI and RL changes over time in the absence of motor impairments in early stages of dopamine depletion may contribute to anticipate PD diagnosis in human patients and to develop early tailored and more effective sex-dependent treatments. |
| publishDate |
2023 |
| dc.date.issued.none.fl_str_mv |
2023-11 |
| dc.date.accessioned.none.fl_str_mv |
2024-01-30T22:21:09Z |
| dc.date.available.none.fl_str_mv |
2024-01-30T22:21:09Z |
| dc.type.none.fl_str_mv |
Trabajo de grado - Doctorado |
| dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
| dc.type.version.none.fl_str_mv |
info:eu-repo/semantics/acceptedVersion |
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http://purl.org/coar/resource_type/c_db06 |
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Text |
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https://purl.org/redcol/resource_type/TD |
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http://purl.org/coar/resource_type/c_db06 |
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acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://hdl.handle.net/1992/73645 |
| dc.identifier.doi.none.fl_str_mv |
10.57784/1992/73645 |
| dc.identifier.instname.none.fl_str_mv |
instname:Universidad de los Andes |
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reponame:Repositorio Institucional Séneca |
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repourl:https://repositorio.uniandes.edu.co/ |
| url |
https://hdl.handle.net/1992/73645 |
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10.57784/1992/73645 instname:Universidad de los Andes reponame:Repositorio Institucional Séneca repourl:https://repositorio.uniandes.edu.co/ |
| dc.language.iso.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.references.none.fl_str_mv |
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Cárdenas Parra, Luis FernandoLievano Parra, Diego JavierBáez Buitrago, Sandra JimenaSabogal, AngelicaFacultad de Ciencias Sociales::Neurociencia y Comportamiento2024-01-30T22:21:09Z2024-01-30T22:21:09Z2023-11https://hdl.handle.net/1992/7364510.57784/1992/73645instname:Universidad de los Andesreponame:Repositorio Institucional Sénecarepourl:https://repositorio.uniandes.edu.co/Background: Motor impairments in Parkinson's disease (PD) are associated with alterations in the prepulse inhibition (PPI) of the acoustic startle response (ASR) and reversal learning (RL) from the early stages of the disease. In this context, animal models enable the exploration of the dynamics of non-motor manifestations associated to dopaminergic depletion in a time-dependent manner. Method: 103 adult male and female Wistar rats received unilateral injections of 6-OHDA or saline into the Substantia Nigra Compacta (SNc). Motor skills and the PPI were assessed before and after surgery. Subsequently, three groups were formed to evaluate action-based RL (AB) and stimulus-based RL (SB). Results: The apomorphine test at 2 weeks confirmed the establishment of dopaminergic depletion. Motor coordination was affected in the lesioned groups, with higher number of grip errors and reduced running speed in lesioned males 6 weeks after surgery. The percentage PPI decreased in lesioned females at 4 weeks but increased in lesioned males 6 weeks after lesioning. Finally, the 6-OHDA lesion did not affect initial discrimination or reversal in the AB task, although a treatment facilitation effect was observed in the reversal of SB task. Additionally, sex-dependent differences were observed in performance. Males showed more perseverative behavior and a higher percentage of the win-stay strategy, while females exhibited slower response latencies for both correct and incorrect responses, displaying a higher percentage of the lose-shift strategy. Conclusion: The results show that subthreshold dopamine depletions in the SNc in the unilateral rodent model of 6-OHDA caused sex-differential effects on PPI and RL with more noticeable motor impairments in males after six weeks after surgery. Further characterization of how PPI and RL changes over time in the absence of motor impairments in early stages of dopamine depletion may contribute to anticipate PD diagnosis in human patients and to develop early tailored and more effective sex-dependent treatments.Vicerrectoría de Investigaciones, Universidad de los Andes. Laboratorio de Neurociencia y Comportamiento. Universidad de los Andes.Doctor en PsicologíaDoctoradoParkinson167 páginasapplication/pdfengUniversidad de los AndesDoctorado en PsicologíaFacultad de Ciencias SocialesDepartamento de PsicologíaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Effects of the unilateral lesion of the substantia nigra compacta with 6-OHDA on reversal learning and prepulse inhibition in male and female Wistar ratsTrabajo de grado - Doctoradoinfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/acceptedVersionhttp://purl.org/coar/resource_type/c_db06Texthttps://purl.org/redcol/resource_type/TDParkinson's diseaseReversal learningPrepulse inhibition6-OHDARatPsicologíaAbbruzzese, G., & Berardelli, A. (2003). Sensorimotor integration in movement disorders. Movement Disorders, 18(3), 231–240. https://doi.org/10.1002/mds.10327Aguirre, C. G., Woo, J. H., Romero-Sosa, J. 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