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

• Published in: Molecular neurobiology Vol. 55; no. 11; pp. 8625 - 8636
• Main Authors: Arroyo-García, Luis Enrique, Vázquez-Roque, Rubén Antonio, Díaz, Alfonso, Treviño, Samuel, De La Cruz, Fidel, Flores, Gonzalo, Rodríguez-Moreno, Antonio
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-11-2018; Springer Nature B.V
• Subjects: Animals; Apomorphine; Apomorphine - pharmacology; Astrocytes; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Dendrites; Dendrites - drug effects; Dendrites - metabolism; Dendritic plasticity; Dopamine; Dopamine D1 receptors; Dopamine D5 receptors; Electrophysiological recording; Excitatory postsynaptic potentials; Glial fibrillary acidic protein; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; Inflammation; Inflammation - pathology; Learning; Long term memory; Long-term potentiation; Long-Term Potentiation - drug effects; Male; Memory - drug effects; Mice; Mice, Inbred C57BL; Motor activity; Movement disorders; Neurobiology; Neurodegenerative diseases; Neurology; Neurons; Neurosciences; Oxidation-Reduction; Oxidative stress; Parkinson's disease; Plasticity; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Receptor mechanisms; Receptors, Dopamine - metabolism; Rodents; Spatial Learning - drug effects; Synaptic plasticity; Synaptic transmission; Learning and memory; Dendritic length; Oxidative stress; Dopamine receptor; Plasticity; Apomorphine; Hippocampus
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-018-0991-2

Apomorphine is a dopamine receptor agonist that activates D
1
–D
5
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.