Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefrontal cortex of adult rats

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RESEARCH PRODUCT

Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefrontal cortex of adult rats

Ramon Guirado Emilio Varea Esther Castillo-gómez María ÁNgeles Gómez-climent Carlos Crespo José Miguel Blasco-ibáñez Juan Nacher Francisco José Martínez-guijarro

subject

Male medicine.medical_specialty Interneuron Dopamine Synaptophysin Prefrontal Cortex Neural Cell Adhesion Molecule L1 Synaptic Transmission Dopamine agonist Rats Sprague-Dawley Developmental Neuroscience Dopamine Dopamine receptor D2 Internal medicine Phenethylamines medicine Animals Neurons Analysis of Variance Microscopy Confocal Neuronal Plasticity Glutamate Decarboxylase Receptors Dopamine D2 Chemistry Dopaminergic Dopamine antagonist Immunohistochemistry Rats medicine.anatomical_structure Endocrinology nervous system Neurology Dopamine receptor Dopamine Agonists Sialic Acids Dopamine Antagonists Haloperidol Neural cell adhesion molecule Neuroscience medicine.drug

description

A "neuroplastic" hypothesis proposes that changes in neuronal structural plasticity may underlie the aetiology of depression and the action of antidepressants. The medial prefrontal cortex (mPFC) is affected by this disorder and shows an intense expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-associated molecule, which is expressed mainly in interneurons. The monoamines serotonin, dopamine and noradrenaline are the principal targets of antidepressant action. Pharmacological manipulation of serotonin levels regulates synaptophysin and PSA-NCAM expression in the adult mPFC. However, the involvement of structural plasticity on the antidepressant effects of dopamine has not been well explored yet. Using immunohistochemistry, we have studied the relationship between dopaminergic fibers and PSA-NCAM expressing neurons in the mPFC and the expression of D2 receptors. In order to evaluate the effects of dopamine in neuronal structural plasticity and on inhibitory neurotransmission, we have analyzed the expression of synaptophysin, PSA-NCAM and GAD67 in the mPFC after cortical dopamine depletion with 6-OHDA and after chronic treatments with the D2 receptor antagonist haloperidol or the D2 receptor agonist PPHT. Many dopaminergic fibers were observed in close apposition to PSA-NCAM expressing neurons and 76% of these cells co-expressed D2 receptor. Both haloperidol treatment and 6-OHDA injection reduced significantly PSA-NCAM, synaptophysin and GAD67 expression in the mPFC. Conversely, PPHT treatment increased the expression of these molecules. Our results give support to the "neuroplastic" hypothesis of depression, suggesting that dopamine acting on D2 receptors may modulate neuronal structural plasticity and inhibitory neurotransmission through changes in PSA-NCAM expression.

year	journal	country	edition	language
2008-11-01	Experimental Neurology

https://doi.org/10.1016/j.expneurol.2008.07.018