Augmenting glutamatergic, but not dopaminergic, activity in the nucleus accumbens shell disrupts responding to a discrete alcohol cue in an alcohol context.
Eur J Neurosci
; 59(7): 1500-1518, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38185906
ABSTRACT
Discrete alcohol cues and contexts are relapse triggers for people with alcohol use disorder exerting particularly powerful control over behaviour when they co-occur. Here, we investigated the neural substrates subserving the capacity for alcohol-associated contexts to elevate responding to an alcohol-predictive conditioned stimulus (CS). Specifically, rats were trained in a distinct 'alcohol context' to respond by entering a fluid port during a discrete auditory CS that predicted the delivery of alcohol and were familiarized with a 'neutral context' wherein alcohol was never available. When conditioned CS responding was tested by presenting the CS without alcohol, we found that augmenting glutamatergic activity in the nucleus accumbens (NAc) shell by microinfusing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) reduced responding to an alcohol CS in an alcohol, but not neutral, context. Further, AMPA microinfusion robustly affected behaviour, attenuating the number, duration and latency of CS responses selectively in the alcohol context. Although dopaminergic inputs to the NAc shell were previously shown to be necessary for CS responding in an alcohol context, here, chemogenetic excitation of ventral tegmental area (VTA) dopamine neurons and their inputs to the NAc shell did not affect CS responding. Critically, chemogenetic excitation of VTA dopamine neurons affected feeding behaviour and elevated c-fos immunoreactivity in the VTA and NAc shell, validating the chemogenetic approach. These findings enrich our understanding of the substrates underlying Pavlovian responding for alcohol and reveal that the capacity for contexts to modulate responding to discrete alcohol cues is delicately underpinned by the NAc shell.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sinais (Psicologia)
/
Núcleo Accumbens
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Neurosci
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá