Changes in the mesocorticolimbic pathway after low dose reserpine-treatment in Wistar and Spontaneously Hypertensive Rat (SHR): implications for cognitive deficits in a progressive animal model for Parkinson’s Disease


Publication type
Article
Language
English
Access rights
Restricted Access
Appears in Collections:
Metrics
Abstract
Reserpine (RES) is an irreversible inhibitor of VMAT2 used to study Parkinson’s disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low dose of reserpine was proposed as a model capable of emulating progressive neurochemical, motor and non-motor impairments in PD. Conversely, compared to Wistar rats, Spontaneously Hypertensive Rats (SHR) are resistant to motor changes induced by repeated treatment with a low dose of RES. However, such resistance has not yet been investigated for RES-induced non-motor impairments. We aimed to assess whether SHR would have differential susceptibility to the object recognition deficit induced by repeated low-dose reserpine treatment. We submitted male Wistar and SHR rats to repeated RES treatment (15 s.c. injections of 0.1 mg/kg, every other day) and assessed object memory acquisition and retrieval 48 h after the 6th RES injection (immediately before the appearance of motor impairments). Only RES Wistar rats displayed memory impairment after reserpine treatment. On the other hand, untreated SHR rats displayed object recognition memory deficit, but RES treatment restored such deficits. We also performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last RES injection. In a different set of animals submitted to the same treatment, we quantified DA, 5-HT and products of lipid peroxidation in the prefrontal cortex (PFC) and hippocampus (HPC). SHR presented increased constitutive levels of DA in the PFC and reduced immunoreactivity to TH in the medial PFC and dorsal HPC. Corroborating the behavioural findings, RES treatment restored those constitutive alterations in SHR. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potentially relevant targets to the study of susceptibility to diseases related to dopaminergic alterations.
Reference
Leão AH.F.F., Meurer YS.R., Freitas TA., Medeiros AM., Abílio VC., Izídio GS., et al. Changes in the mesocorticolimbic pathway after low dose reserpine-treatment in Wistar and Spontaneously Hypertensive Rat (SHR): implications for cognitive deficits in a progressive animal model for Parkinson’s Disease. Behav Brain Res. 2021 May;in press:113349. doi:10.1016/j.bbr.2021.113349.
Link to cite this reference
https://repositorio.butantan.gov.br/handle/butantan/3731
Issue Date
2021


Files in This Item:

Existing users please Login
10.1016j.bbr.2021.113349.pdf
Description:
Size: 4.26 MB
Format: Adobe PDF
Embargoed until January 1, 2999    Request a copy
Show full item record

The access to the publications deposited in this repository respects the licenses from journals and publishers.