Hypocretin/orexin knock-out mice display disrupted behavioral and dopamine responses to cocaine.
Addict Biol
; 22(6): 1695-1705, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-27480648
ABSTRACT
The hypocretin/orexin (HCRT) system is implicated in reward and reinforcement processes through actions on the mesolimbic dopamine (DA) system. Here we provide evidence for the relationship between HCRT and DA in vivo in anesthetized and freely moving mice. The ability of cocaine to elicit reward-related behaviors in mice lacking the HCRT prepro-peptide (HCRT knock-out; KO) and wild-type controls was determined using conditioned place preference. Using a combination of microdialysis and in vivo fast scan cyclic voltammetry in anesthetized and freely moving mice, we investigated the underlying role of HCRT in the regulation of DA release and uptake. We show that, unlike wild-type mice, HCRT KO mice fail to develop characteristic conditioned place preference for cocaine. These mice also demonstrated reduced DA release and uptake under baseline conditions in both anesthetized and freely moving experiments. Further, diminished DA signaling in HCRT KO mice persists following administration of cocaine. These findings indicate that HCRT is essential for the expression of behaviors associated with the rewarding effects of cocaine, and suggest that HCRT regulation of reward and reinforcement may be related to disruptions to DA neurotransmission.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Comportamento Animal
/
Dopamina
/
Cocaína
/
Inibidores da Captação de Dopamina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Addict Biol
Assunto da revista:
TRANSTORNOS RELACIONADOS COM SUBSTANCIAS
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos