The role of corticotrophin-releasing factor in stress-induced relapse to alcohol-seeking behavior in rats

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.

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Inclusive Leadership and Creative Performance : The Role of Psychological Safety, Feedback-Seeking Behavior, and Power-Distance

Korean Journal of Resources Development ◽

10.24991/kjhrd.2019.12.22.4.181 ◽

2019 ◽

Vol 22 (4) ◽

pp. 181-205 ◽

Cited By ~ 3

Author(s):

Mikyoung Kim ◽

Jaeseung Moon

Keyword(s):

Power Distance ◽

Psychological Safety ◽

Creative Performance ◽

Feedback Seeking ◽

Inclusive Leadership ◽

Seeking Behavior

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Faculty Opinions recommendation of Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732647279.793544896 ◽

2018 ◽

Author(s):

Dorit Ron

Keyword(s):

Seeking Behavior ◽

Alcohol Seeking

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mTORC and PKCε in Regulation of Alcohol Use Disorder

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200624122325 ◽

2020 ◽

Vol 20 (17) ◽

pp. 1696-1708 ◽

Cited By ~ 1

Author(s):

Athirah Hanim ◽

Isa Naina Mohamed ◽

Rashidi M. Pakri Mohamed ◽

Srijit Das ◽

Norefrina Shafinaz Md Nor ◽

...

Keyword(s):

Alcohol Use ◽

Alcohol Use Disorder ◽

Alcohol Intake ◽

Potential Role ◽

Synaptic Proteins ◽

Cellular Mechanisms ◽

Kinase C ◽

Protein Kinase C Epsilon ◽

Seeking Behavior

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

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