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The Effects of Non-selective Dopamine Receptor Activation by Apomorphine in the Mouse Hippocampus

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Abstract

Apomorphine is a dopamine receptor agonist that activates D1–D5 dopamine receptors and that is used to treat Parkinson’s disease (PD). However, the effect of apomorphine on non-motor activity has been poorly studied, and likewise, the effects of dopaminergic activation in brain areas that do not fulfill motor functions are unclear. The aim of this study was to determine how dopamine receptor activation affects behavior, as well as plasticity, morphology, and oxidative stress in the hippocampus. Adult mice were chronically administered apomorphine (1 mg/kg for 15 days), and the effects on memory and learning, synaptic plasticity, dendritic length, inflammatory responses, and oxidative stress were evaluated. Apomorphine impaired learning and long-term memory in mice, as evaluated in the Morris water maze test. In addition, electrophysiological recording of field excitatory postsynaptic potentials (fEPSP) indicated that the long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus was fully impaired by apomorphine. In addition, a Sholl analysis of Golgi-Cox stained neurons showed that apomorphine reduced the total length of dendrites in the CA1 region of the hippocampus. Finally, there were more reactive astrocytes and oxidative stress biomarkers in mice administered apomorphine, as measured by GFAP immunohistochemistry and markers of redox balance, respectively. Hence, the non-selective activation of dopaminergic receptors in the hippocampus by apomorphine triggers deficiencies in learning and memory, it prevents LTP, reduces dendritic length, and provokes neuronal damage.

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Acknowledgements

We acknowledge the assistance of Dr. Mark Sefton in the preparation of this manuscript and the technical assistance of Dr. Yuniesky Andrade-Talavera. This work received financial support from the following grants: AR-M (MINECO/FEDER BFU2012-38208 and the Junta de Andalucía P11-CVI-7290) and GF (VIEP-BUAP Number FLAG-2016 and CONACYT Number 252808).

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Authors and Affiliations

  1. Laboratorio de Neurociencia Celular y Plasticidad, Universidad Pablo de Olavide, Sevilla, Spain

    Luis Enrique Arroyo-García & Antonio Rodríguez-Moreno

  2. Laboratorio de Fisiología de la Conducta, Instituto Politécnico Nacional, Mexico City, Mexico

    Luis Enrique Arroyo-García & Fidel De La Cruz

  3. Laboratorio de Neuropsiquiatría, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, 14 Sur 6301, 72570, Puebla, CP, Mexico

    Luis Enrique Arroyo-García, Rubén Antonio Vázquez-Roque & Gonzalo Flores

  4. Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

    Alfonso Díaz & Samuel Treviño

  5. Laboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, 41013, Sevilla, Spain

    Antonio Rodríguez-Moreno

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  1. Luis Enrique Arroyo-García
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  2. Rubén Antonio Vázquez-Roque
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  3. Alfonso Díaz
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Correspondence to Gonzalo Flores or Antonio Rodríguez-Moreno.

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Arroyo-García, L.E., Vázquez-Roque, R.A., Díaz, A. et al. The Effects of Non-selective Dopamine Receptor Activation by Apomorphine in the Mouse Hippocampus. Mol Neurobiol 55, 8625–8636 (2018). https://doi.org/10.1007/s12035-018-0991-2

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