Paroxetine and Low-dose Risperidone Induce Serotonin 5-HT1A and Dopamine D2 Receptor Heteromerization in the Mouse Prefrontal Cortex.
Neuroscience
; 377: 184-196, 2018 05 01.
Article
em En
| MEDLINE
| ID: mdl-29544901
ABSTRACT
Recently, it has been shown that serotonin 5-HT1A receptor interacts with dopamine D2 receptor in vitro. However, the existence of 5-HT1A-D2 heteromers in native tissue remains unexplored. In the present study, we investigated 5-HT1A-D2 receptor heteromerization in mice treated acutely or chronically with paroxetine (10â¯mg/kg) or risperidone (0.05â¯mg/kg). Receptor heteromerization was visualized and quantified in the mouse brain by in situ proximity ligation assay (PLA). Additionally, we aimed to determine the cellular localization of 5-HT1A-D2 receptor heteromers in mouse adult primary neuronal cells by immunofluorescent staining with markers for astrocytes (GFAP) and neurons (NeuN and MAP2). The results from the current study demonstrated that 5-HT1A and D2 receptor co-localization and heteromerization occurred in the mouse prefrontal cortex. Counterstaining after PLA confirmed neuronal (pyramidal and GABAergic) as well as astrocytal localization of 5-HT1A-D2 receptor heteromers. Chronic administration of paroxetine or risperidone increased the level of 5-HT1A-D2 receptor heteromers in the prefrontal cortex. These changes were not accompanied by any changes in the expression of mRNAs (measured by in situ hybridization) or densities of 5-HT1A and D2 receptors (quantified by receptor autoradiography with [3H]8-OH-DPAT and [3H]domperidone, respectively), what all indicated that paroxetine and risperidone facilitated 5-HT1A-D2 heteromer formation independently of the receptor expression. In vitro homogenous time-resolved FRET (HTRF) study confirmed the ability of tested drugs to influence the human 5-HT1A-D2 heteromer formation. The obtained data indicate that the increase in 5-HT1A-D2 receptor heteromerization is a common molecular characteristic of paroxetine and low-dose risperidone treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Dopamina D2
/
Córtex Pré-Frontal
/
Paroxetina
/
Neurotransmissores
/
Risperidona
/
Receptor 5-HT1A de Serotonina
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Neuroscience
Ano de publicação:
2018
Tipo de documento:
Article