Activation and blockade of serotonin4 receptors in the lateral habenula improve working memory in unilateral 6-hydroxydopamine-lesioned Parkinson's rats.
Neurol Res
; 41(7): 585-593, 2019 Jul.
Article
en En
| MEDLINE
| ID: mdl-30929589
ABSTRACT
Objective:
The aim of the present study was to investigate the effects and mechanism of 6-hydroxydopamine (6-OHDA) lesions and serotonin 4 (5-HT4) receptors in the lateral habenula (LHb) on Parkinson's disease (PD) related working memory.Methods:
The working memory was measured by the T-maze rewarded alternation test in sham rats and rats with unilateral 6-OHDA lesions of substantia nigra pars compacta (SNc). The concentrations of dopamine (DA), noradrenaline (NA) and 5-HT in the related brain regions were measured by neurochemistry.Results:
The results showed that 6-OHDA lesions of the SNc induced working memory impairment. Intra-LHb injection of 5-HT4 receptor agonist BIMU-8 (2, 4 or 8 µg) and antagonist GR113808 (1, 3.3 or 10 µg) improved the working memory only in the lesioned rats. Intra-LHb injection of BIMU-8 (8 µg) significantly increased DA levels in the medial prefrontal cortex, dorsal hippocampus and amygdala in the lesioned rats but not in sham rats. BIMU-8 did not change NA and 5-HT levels in the related brain regions in both sham and lesioned rats. Intra-LHb injection of GR113808 (10 µg) changed DA, NA and 5-HT levels in related brain regions in both sham and the lesioned rats. In addition, the 5-HT4 receptor-positive neurons in the LHb increased significantly in the lesioned rats.Conclusion:
These findings suggested that unilateral lesions of the SNc induced working memory impairment and up-regulation of 5-HT4 receptors in the LHb. Activation and blockade of LHb 5-HT4 receptors improved working memory, that were related to the change of monoamines levels. Abbreviation 6-OHDA 6-hydroxydopamine; serotonin5-HT; LHb lateral habenula; PD Parkinson's disease; SNc substantia nigra pars compacta; DA dopamine; NA noradrenaline.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Habénula
/
Trastornos Parkinsonianos
/
Receptores de Serotonina 5-HT4
/
Memoria a Corto Plazo
Límite:
Animals
Idioma:
En
Revista:
Neurol Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
China