Orexin-1 receptor signaling within the lateral hypothalamus, but not bed nucleus of the stria terminalis, mediates context-induced relapse to alcohol seeking

Background: The lateral hypothalamic orexin (hypocretin) system has a well-established role in the motivation for reward. This has particular relevance to substance use disorders since orexin-1 receptors play a critical role in alcohol-seeking behavior, acting at multiple nodes in relapse-associated...

Full description

Saved in:
Bibliographic Details
Published in:Journal of psychopharmacology (Oxford) 2020-11, Vol.34 (11), p.1261-1270
Main Authors: Campbell, Erin J, Hill, Mitchell KRI, Maddern, Xavier J, Jin, Shubo, Pang, Terence Y, Lawrence, Andrew J
Format: Article
Language:English
Subjects:
Alcohol
Alcohol use
Brain
Footshock
Hypothalamus
Hypothalamus (lateral)
Inbreeding
Motivation
Orexin receptors
Orexins
Punishment
Reinforcement
Stria terminalis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: The lateral hypothalamic orexin (hypocretin) system has a well-established role in the motivation for reward. This has particular relevance to substance use disorders since orexin-1 receptors play a critical role in alcohol-seeking behavior, acting at multiple nodes in relapse-associated networks. Aims: This study aimed to further our understanding of the role of orexin-1 receptor signaling within the lateral hypothalamus and bed nucleus of the stria terminalis, specifically in context-induced relapse to alcohol-seeking following punishment-imposed abstinence. Methods: We trained inbred male alcohol-preferring rats to self-administer alcohol in one environment or context (Context A) and subsequently punished their alcohol-reinforced lever presses in a different environment (Context B) using contingent foot shock punishment. Finally, we tested rats for relapse-like behavior in either context following systemic, intra-lateral hypothalamus or intra-bed nucleus of the stria terminalis orexin-1 receptor antagonism with SB-334867. Results/outcomes: We found that systemic orexin-1 receptor antagonism significantly reduced alcohol-seeking in both contexts. Intra-lateral hypothalamus orexin-1 receptor antagonism significantly reduced alcohol-seeking in Context A whereas intra-bed nucleus of the stria terminalis orexin-1 receptor antagonism had no effect on alcohol-seeking behavior. Conclusions/interpretation: Our results suggest a role for the orexin-1 receptor system in context-induced relapse to alcohol-seeking. Specifically, intra-lateral hypothalamus orexin microcircuits contribute to alcohol-seeking.
ISSN:0269-8811
1461-7285
DOI:10.1177/0269881120959638