title: Dopamine receptor D5 deficiency results in a selective reduction of hippocampal NMDA receptor subunit NR2B expression and impaired memory.
abstract: Pharmacological evidence associates type I dopamine receptors, including subtypes D1 and D5, with learning and memory. Analyses using genetic approaches have determined the relative contribution of dopamine receptor D1 (D1R) in cognitive tasks. However, the lack of drugs that can discriminate between D1R and D5R has made the pharmacological distinction between the two receptors difficult. Here, we aimed to determine the role of D5R in learning and memory. In this study we tested D5R knockout mice and wild-type littermates in a battery of behavioral tests, including memory, attention, locomotion, anxiety and motivational evaluations. Our results show that genetic deficiency of D5R significantly impairs performance in the Morris water maze paradigm, object location and object recognition memory, indicating a relevant role for D5R in spatial memory and recognition memory. Moreover, the lack of D5R resulted in decreased exploration and locomotion. In contrast, D5R deficiency had no impact on working memory, anxiety and depressive-like behavior, measured using the spontaneous alternation, open-field, tail suspension test, and forced swimming test. Electrophysiological analyses performed on hippocampal slices showed impairment in long-term-potentiation in mice lacking D5R. Further analyses at the molecular level showed that genetic deficiency of D5R results in a strong and selective reduction in the expression of the NMDA receptor subunit NR2B in the hippocampus. These findings demonstrate the relevant contribution of D5R in memory and suggest a functional interaction of D5R with hippocampal glutamatergic pathways.
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Andres Bello, 8370146, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Moraga-Amaro
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272, Santiago, Chile.
authors.forename: Hugo
authors.initials: H
authors.lastname: González
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272, Santiago, Chile.
authors.forename: Valentina
authors.initials: V
authors.lastname: Ugalde
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Andres Bello, 8370146, Santiago, Chile.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Donoso-Ramos
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Andres Bello, 8370146, Santiago, Chile.
authors.forename: Daisy
authors.initials: D
authors.lastname: Quintana-Donoso
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, 9170022, Santiago, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Lara
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, 9170022, Santiago, Chile.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Morales
authors.affiliation: Laboratorio de Neurociencias, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, 9170022, Santiago, Chile.
authors.forename: Patricio
authors.initials: P
authors.lastname: Rojas
authors.affiliation: Laboratorio de Neuroinmunología, Fundación Ciencia & Vida, Ñuñoa, 7780272, Santiago, Chile; Laboratorio de Neuroinmunología, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas, Universidad Andres Bello, 8370146, Santiago, Chile. Electronic address: rpacheco@cienciavida.org.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pacheco
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Andres Bello, 8370146, Santiago, Chile. Electronic address: jstehberg@unab.cl.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Stehberg
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001288:Attention / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation; D008297:Male; D008568:Memory / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D050641:Receptors, Dopamine D5 / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D050641:Receptors, Dopamine D5
keywords: Dopamine receptor D5; Knockout mice; Long-term potentiation; N-methyl-d-aspartate receptors; Spatial memory; Synaptic plasticity