Therapeutic Effects of Quetiapine and 5-HT1A Receptor Agonism on Hyperactivity in Dopamine-Deficient Mice.
Int J Mol Sci
; 23(13)2022 Jul 04.
Article
en En
| MEDLINE
| ID: mdl-35806448
ABSTRACT
Some diseases that are associated with dopamine deficiency are accompanied by psychiatric symptoms, including Parkinson's disease. However, the mechanism by which this occurs has not been clarified. Previous studies found that dopamine-deficient (DD) mice exhibited hyperactivity in a novel environment. This hyperactivity is improved by clozapine and donepezil, which are used to treat psychiatric symptoms associated with dopamine deficiency (PSDD). We considered that DD mice could be used to study PSDD. In the present study, we sought to identify the pharmacological mechanism of PSDD. We conducted locomotor activity tests by administering quetiapine and drugs that have specific actions on serotonin (5-hydroxytryptamine [5-HT]) receptors and muscarinic receptors. Changes in neuronal activity that were induced by drug administration in DD mice were evaluated by examining Fos immunoreactivity. Quetiapine suppressed hyperactivity in DD mice while the 5-HT1A receptor antagonist WAY100635 inhibited this effect. The number of Fos-positive neurons in the median raphe nucleus increased in DD mice that exhibited hyperactivity and was decreased by treatment with quetiapine and 5-HT1A receptor agonists. In conclusion, hyperactivity in DD mice was ameliorated by quetiapine, likely through 5-HT1A receptor activation. These findings suggest that 5-HT1A receptors may play a role in PSDD, and 5-HT1A receptor-targeting drugs may help improve PSDD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antipsicóticos
/
Dopamina
/
Receptor de Serotonina 5-HT1A
/
Agonistas del Receptor de Serotonina 5-HT1
/
Fumarato de Quetiapina
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón