A D2 to D1 shift in dopaminergic inputs to midbrain 5-HT neurons causes anorexia in mice.
Nat Neurosci
; 25(5): 646-658, 2022 05.
Article
em En
| MEDLINE
| ID: mdl-35501380
ABSTRACT
Midbrain dopamine (DA) and serotonin (5-HT) neurons regulate motivated behaviors, including feeding, but less is known about how these circuits may interact. In this study, we found that DA neurons in the mouse ventral tegmental area bidirectionally regulate the activity of 5-HT neurons in the dorsal raphe nucleus (DRN), with weaker stimulation causing DRD2-dependent inhibition and overeating, while stronger stimulation causing DRD1-dependent activation and anorexia. Furthermore, in the activity-based anorexia (ABA) paradigm, which is a mouse model mimicking some clinical features of human anorexia nervosa (AN), we observed a DRD2 to DRD1 shift of DA neurotransmission on 5-HTDRN neurons, which causes constant activation of these neurons and contributes to AN-like behaviors. Finally, we found that systemic administration of a DRD1 antagonist can prevent anorexia and weight loss in ABA. Our results revealed regulation of feeding behavior by stimulation strength-dependent interactions between DA and 5-HT neurons, which may contribute to the pathophysiology of AN.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dopamina
/
Serotonina
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos