title: Dopamine receptor D3 deficiency results in chronic depression and anxiety.
abstract: Over the last decade accumulating evidence suggests that brain dopamine (DA) has a role in depression, particularly given the high comorbidity of depression with Parkinson's Disease (PD) and the antidepressant effects of the DA receptor subtype 3 (D3R) agonist pramipexole. The present study assesses the role of D3R in depression. Here we hypothesized that D3R mediates the antidepressant effects of DA. Thus, genetic deficiency of D3R in D3R knockout (D3RKO) mice would yield animals with chronic depressive symptoms. Whereas D3R deficient mice did not show significant alterations in locomotion when tested in the openfield, these animals showed anxiety-like symptoms measured as a significant increase in thigmotaxis at the openfield and a significantly lower time spent in the lit compartment at the light/dark exploration test. D3RKO animals also showed depressive-like symptoms as measured by increased immobility time in the Porsolt forced swim test and the tail suspension test, as well as anhedonia measured in the non-motor dependent sucrose test. In conclusion, D3R deficiency results in anxiety-like and depressive-like symptoms that cannot be attributed to motor dysfunction.
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Andres Bello, Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Moraga-Amaro
authors.affiliation: Laboratorio of Neuroinmunología, Fundación Ciencia & Vida, Av. Zañartu 1482, Ñuñoa (7780272), Santiago, Chile.
authors.forename: Hugo
authors.initials: H
authors.lastname: Gonzalez
authors.affiliation: Laboratorio of Neuroinmunología, Fundación Ciencia & Vida, Av. Zañartu 1482, Ñuñoa (7780272), Santiago, Chile; Programa de Biomedicina, Universidad San Sebastián, Av. Zañartu 1482, Ñuñoa (7780272), Santiago, Chile.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Pacheco
authors.affiliation: Laboratorio de Neurobiología, Centro de Investigaciones Biomédicas, Universidad Andres Bello, Santiago, Chile. Electronic address: stehberg@unab.cl.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Stehberg
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000503:physiopathology; D002908:Chronic Disease; D003623:Dark Adaptation / Q000235:genetics; D003863:Depression / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005518:Food Preferences / Q000523:psychology; D019417:Hindlimb Suspension; D046353:Immobility Response, Tonic / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011930:Reaction Time / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000172:deficiency* / Q000235:genetics; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming
chemical_list: D050637:Receptors, Dopamine D3; D013395:Sucrose
keywords: Anxiety; Behavior; Depression; Dopamine receptor D3; Knockout mice; Locomotor function