Corticotropin releasing hormone receptor 1 in the medial prefrontal cortex mediates aversion resistant alcohol intake.
Alcohol
Aversion
CRH
CRHR1
Corticotropin releasing hormone
Prefrontal cortex
Sex difference
Journal
Psychopharmacology
ISSN: 1432-2072
Titre abrégé: Psychopharmacology (Berl)
Pays: Germany
ID NLM: 7608025
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
01
07
2024
accepted:
18
10
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
aheadofprint
Résumé
Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed. We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake. We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake. After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment. Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking.
Identifiants
pubmed: 39466414
doi: 10.1007/s00213-024-06707-5
pii: 10.1007/s00213-024-06707-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAAA NIH HHS
ID : R03 AA026989
Pays : United States
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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