Cocaine disrupts action flexibility via glucocorticoid receptors.
iScience
; 27(7): 110148, 2024 Jul 19.
Article
en En
| MEDLINE
| ID: mdl-38989467
ABSTRACT
Many addictive drugs increase stress hormone levels. They also alter the propensity of organisms to prospectively select actions based on long-term consequences. We hypothesized that cocaine causes inflexible action by increasing circulating stress hormone levels, activating the glucocorticoid receptor (GR). We trained mice to generate two nose pokes for food and then required them to update action-consequence associations when one response was no longer reinforced. Cocaine delivered in adolescence or adulthood impaired the capacity of mice to update action strategies, and inhibiting CORT synthesis rescued action flexibility. Next, we reduced Nr3c1, encoding GR, in the orbitofrontal cortex (OFC), a region of the brain responsible for interlacing new information into established routines. Nr3c1 silencing preserved action flexibility and dendritic spine abundance on excitatory neurons, despite cocaine. Spines are often considered substrates for learning and memory, leading to the discovery that cocaine degrades the representation of new action memories, obstructing action flexibility.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
IScience
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos