Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-Induced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala

Nelson, Britta S.; Fulenwider, Hannah D.; Nennig, Sadie E.; Smith, Britessia M.; Sequeira, Michelle K.; Chimberoff, Scott H.; Richie, Christopher T.; Cheng, Kejun; Rice, Kenner C.; Harvey, Brandon K.; Heilig, Markus; Schank, Jesse R.

doi:10.1016/j.neuroscience.2019.06.023

Cited by 18 publications

(16 citation statements)

References 47 publications

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“…Antagonism of NK1R and KO mice reduces alcohol consumption 127 and Antagonism of NK1R decreases alcohol self-administration in alcohol-preferring rats 128 . Furthermore, adeno-associated virus-mediated overexpression of NK1R in the central amygdala increased alcohol self-administration 129 , which is consistent with our finding. A Family-based association study in human genetics have also reported NK3R is associated with alcohol and cocaine dependence 130 .…”

Section: Discussionsupporting

confidence: 92%

Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans

Salim

Kan

Batsaikhan

et al. 2022

Sci Rep

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Despite the catastrophic consequences of alcohol abuse, alcohol use disorders (AUD) and comorbidities continue to strain the healthcare system, largely due to the effects of alcohol-seeking behavior. An improved understanding of the molecular basis of alcohol seeking will lead to enriched treatments for these disorders. Compulsive alcohol seeking is characterized by an imbalance between the superior drive to consume alcohol and the disruption or erosion in control of alcohol use. To model the development of compulsive engagement in alcohol seeking, we simultaneously exploited two distinct and conflicting Caenorhabditis elegans behavioral programs, ethanol preference and avoidance of aversive stimulus. We demonstrate that the C. elegans model recapitulated the pivotal features of compulsive alcohol seeking in mammals, specifically repeated attempts, endurance, and finally aversion-resistant alcohol seeking. We found that neuropeptide signaling via SEB-3, a CRF receptor-like GPCR, facilitates the development of ethanol preference and compels animals to seek ethanol compulsively. Furthermore, our functional genomic approach and behavioral elucidation suggest that the SEB-3 regulates another neuropeptidergic signaling, the neurokinin receptor orthologue TKR-1, to facilitate compulsive ethanol-seeking behavior.

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Section: Discussionsupporting

confidence: 92%

Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans

Salim

Kan

Batsaikhan

et al. 2022

Sci Rep

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“…The Mir20b and anti- Mir20b were cloned into the pOTTC385-pAAV CMV-IE IRES EGFP vector (Addgene plasmid # 102936) ( Nelson et al, 2019 ) and co-transfected with pAAV-DJ vector and pAAV-Helper vector into HEK 293T cells to generate recombinant adeno-associated virus expressing Mir20b or anti- Mir20b according to the manufacturer’s protocol (Cell Biolabs, San Diego, CA). The AAVs were purified with AAVpro Purification Kit (Takara Bio, Shiga, Japan).…”

Section: Methodsmentioning

confidence: 99%

Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA

Lee

Jang

Kim

et al. 2021

eLife

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Background:Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver. Although nuclear receptors (NRs) play a crucial role in hepatic lipid metabolism, the underlying mechanisms of NR regulation in NAFLD remain largely unclear. Methods:Using network analysis and RNA-seq to determine the correlation between NRs and microRNA in human NAFLD patients, we revealed that MIR20B specifically targets PPARA. MIR20B mimic and anti-MIR20B were administered to human HepG2 and Huh-7 cells and mouse primary hepatocytes as well as high fat diet (HFD)- or methionine-deficient diet (MCD)-fed mice to verify the specific function of MIR20B in NAFLD. We tested the inhibition of the therapeutic effect of a PPARα agonist, fenofibrate, by Mir20b and the synergic effect of combination of fenofibrate with anti-Mir20b in NAFLD mouse model. Results:We revealed that MIR20B specifically targets PPARA through miRNA regulatory network analysis of nuclear receptor genes in NAFLD. The expression of MIR20B was upregulated in free fatty acid (FA)-treated hepatocytes and the livers of both obesity-induced mice and NAFLD patients. Overexpression of MIR20B significantly increased hepatic lipid accumulation and triglyceride levels. Furthermore, MIR20B significantly reduced FA oxidation and mitochondrial biogenesis by targeting PPARA. In Mir20b-introduced mice, the effect of fenofibrate to ameliorate hepatic steatosis was significantly suppressed. Finally, inhibition of Mir20b significantly increased FA oxidation and uptake, resulting in improved insulin sensitivity and a decrease in NAFLD progression. Moreover, combination of fenofibrate and anti-Mir20b exhibited the synergic effect on improvement of NAFLD in MCD-fed mice. Conclusions:Taken together, our results demonstrate that the novel MIR20B targets PPARA, plays a significant role in hepatic lipid metabolism, and present an opportunity for the development of novel therapeutics for NAFLD. Funding:This research was funded by Korea Mouse Phenotyping Project (2016M3A9D5A01952411), the National Research Foundation of Korea (NRF) grant funded by the Korea government (2020R1F1A1061267, 2018R1A5A1024340, NRF-2021R1I1A2041463, 2020R1I1A1A01074940), and the Future-leading Project Research Fund (1.210034.01) of UNIST.

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“…Additionally, intra-CeA administration of an NK 1 R antagonist reduced alcohol self-administration and stress-induced alcohol seeking in alcohol-preferring rats (Nelson et al, 2019;Schank et al, 2013), while viral over-expression of NK 1 R in the CeA of Wistar rats enhanced stress-induced alcohol seeking (Nelson et al, 2019) (Table 2). In the CeM of naïve rats, SP increased GABAergic transmission, suggesting an enhancement of inhibitory CeM tone (Khom, Steinkellner, et al, 2020).…”

Section: Tachykininsmentioning

confidence: 99%

A balancing act: the role of pro‐ and anti‐stress peptides within the central amygdala in anxiety and alcohol use disorders

Walker

2021

Journal of Neurochemistry

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Abbreviations: 2-AG, 2-arachidonoylglycerol; 5-HT 1A , serotonin 1A receptor; 5-HT 1B , serotonin 1A receptor; 5-HT 2A (Htr2a), serotonin 2A receptor; 5-HT 3 , serotonin 3 receptor; AEA, anandamide; AR, adrenoceptors; AUD, alcohol use disorder; BA, basal nucleus of the amygdala; BLA, basolateral nucleus of the amygdala; BMA, basomedial nucleus of the amygdala; BNST, bed nucleus of the stria terminalis; CALCRL (Calcrl), calcitonin receptor-like; CART (Cartpt), cocaine and amphetamine regulated transcript; CB 1 , cannabinoid type 1; CB 2 , cannabinoid type 2; CeA, central nucleus of the amygdala; CeC, capsular division of the CeA; CeL, lateral division of the CeA; CeM, medial division of the CeA; CNS, central nervous system; CoA, cortical nucleus of the amygdala; CRF (Crh), corticotrophin releasing factor; CRF 1 (Crhr1), CRF receptor 1; D 1 R (Drd1), dopamine D1 receptor; D 2 R (Drd2), dopamine D2 receptor; EGFP, enhanced green fluorescent protein; FAAH, fatty acid amide hydrolase; FISH, fluorescent in-situ hybridization; GAL 1 , galanin 1 receptor; GAL 2 , galanin 2 receptor; GAL 3 , galanin 3 receptor; GPCR, G protein-coupled receptors; HPA, hypothalamic-pituitary-adrenal axis; IEG, early immediate gene; IHC, immunohistochemistry; IPSC, inhibitory postsynaptic potentials; ITC, intercalated cells of the amygdala; KO, knockout; LA, lateral basal nucleus of the amygdala; LC, locus coeruleus; LDB, light-dark box LH, lateral hypothalamus; MAGL, monoacylglycerol lipase; MeA, medial nucleus of the amygdala; mSP, Marchigian Sardinian alcohol-preferring rat; N/O-FQ

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Escalated Alcohol Self-Administration and Sensitivity to Yohimbine-Induced Reinstatement in Alcohol Preferring Rats: Potential Role of Neurokinin-1 Receptors in the Amygdala

Cited by 18 publications

References 47 publications

Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans

Neuropeptidergic regulation of compulsive ethanol seeking in C. elegans

Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA

A balancing act: the role of pro‐ and anti‐stress peptides within the central amygdala in anxiety and alcohol use disorders

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