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Pharmacological or genetic blockade of the dopamine D3 receptor increases cell proliferation in the hippocampus of adult mice
Author(s) -
Egeland Martin,
Zhang Xiaoqun,
Millan Mark J.,
Mocaer Elisabeth,
Svenningsson Per
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12011
Subject(s) - neurogenesis , subventricular zone , dopamine receptor d3 , biology , subgranular zone , dentate gyrus , neuroscience , receptor , doublecortin , dopamine , dopamine receptor , medicine , endocrinology , hippocampal formation , microbiology and biotechnology , neural stem cell , stem cell , biochemistry
Dopamine plays an important role in cellular processes controlling the functional and structural plasticity of neurons, as well as their generation and proliferation, both in the developing and the adult brain. The precise roles of individual dopamine receptors subtypes in adult neurogenesis remain poorly defined, although D3 receptors are known to be involved in neurogenesis in the subventricular zone. By contrast, very few studies have addressed the influence of dopamine and D3 receptors upon neurogenesis in the subgranular zone of the hippocampus, an issue addressed herein employing constitutive D3 receptor knockout mice, or chronic exposure to the preferential D3 receptor antagonist, S33138. D3 receptor knockout mice revealed increased baseline levels of cell proliferation and ongoing neurogenesis, as measured both using Ki‐67 and doublecortin, whereas there was no difference in cell survival as measured by BrdU (5‐bromo‐2′‐deoxyuridine). Chronic administration of S33138 was shown to be functionally active in enhancing levels of the plasticity‐related molecule, delta‐FosB, in the D3 receptor‐rich nucleus accumbens. In accordance with the stimulated neurogenesis seen in D3 receptor knockout mice, S33138 increased proliferation in wild‐type mice. These observations suggest that D3 receptors exert a tonic, constitutive inhibitory influence upon adult hippocampal neurogenesis.