title: Dopamine receptor dysregulation in hippocampus of aged rats underlies chronic pulsatile L-Dopa treatment induced cognitive and emotional alterations.
abstract: L-Dopa is the major symptomatic therapy for Parkinson's disease, which commonly occurs in elderly patients. However, the effects of chronic use on mood and cognition in old subjects remain elusive. In order to compare the effects of a chronic pulsatile L-Dopa treatment on emotional and cognitive functions in young (3 months) and old (18 months) intact rats, an L-Dopa/carbidopa treatment was administered every 12 h over 4 weeks. Rats were assessed for behavioural despair (repeated forced swimming test, RFST), anhedonia (sucrose preference test, SPT) and spatial learning (Morris water maze, MWM) in the late phase of treatment (T). Neuronal expression of Fos in the hippocampus at the early and late phases of T, as well as after MWM was studied. The density and ratio of dopamine D5r, D3r and D2r receptors were also evaluated in the hippocampus using immunohistochemistry and confocal microscopy. Young rats showed similar patterns during behavioural tests, whereas aged treated rats showed increased immobility counts in RFST, diminished sucrose liquid intake in SPT, and spatial learning impairment during MWM. Fos expression was significantly blunted in the aged treated group after MWM. The density of D5r, D3r and D2r was increased in both aged groups. The treatment reduced the ratio of D5r/D3r and D5r/D2r in both groups. Moreover, aged treated subjects had significant lower values of D5r/D3r and higher values of D5r/D2r when compared with young treated subjects. These results indicate that chronic L-Dopa treatment in itself could trigger emotional and cognitive dysfunctions in elderly subjects through dopamine receptor dysregulation.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México 04510, D. F, México.
authors.forename: Vito S
authors.initials: VS
authors.lastname: Hernández
authors.affiliation: Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.
authors.forename: Sonia
authors.initials: S
authors.lastname: Luquín
authors.affiliation: Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México.
authors.forename: Fernando
authors.initials: F
authors.lastname: Jáuregui-Huerta
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México 04510, D. F, México; Facultad de Nutrición, Universidad Veracruzana, Xalapa, México.
authors.forename: Aleph A
authors.initials: AA
authors.lastname: Corona-Morales
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México 04510, D. F, México.
authors.forename: Mauricio P
authors.initials: MP
authors.lastname: Medina
authors.affiliation: Instituto de Investigaciones en Matemáticas Aplicadas y de Sistemas, Universidad Nacional Autónoma de México, México 04510, D. F, México.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ruíz-Velasco
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México 04510, D. F, México. Electronic address: limei@unam.mx.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D059445:Anhedonia / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002230:Carbidopa / Q000009:adverse effects*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D004338:Drug Combinations; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D050641:Receptors, Dopamine D5 / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects / Q000502:physiology
chemical_list: D000978:Antiparkinson Agents; D004338:Drug Combinations; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C009265:carbidopa, levodopa drug combination; D050641:Receptors, Dopamine D5; D007980:Levodopa; D002230:Carbidopa
keywords: Anhedonia; D2r; D3r; D5r; Depression; Learning and memory; Palliative care in Parkinson's disease