Orexin- 1 signaling within the lateral hypothalamus, but not bed nucleus of the stria terminalis, mediates context-induced relapse to alcohol seeking
Campbell, E.J, Hill, M.K.R.I, Maddern, X.J, Jin, S, Pang, T.Y, Lawrence, A.J.
Journal of Psychopharmacology - 2020
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.
Keywords: Context; alcohol use disorder; bed nucleus of the stria terminalis; lateral hypothalamus; orexin; punishment.