Orexin receptor blockers: A tool for lowering alcohol intake and alcohol addictive behavior in the light of preclinical studies

Antagonist	In vitro study (Cellular measurements)	In vivo (Proven action)	Procedure	Dose/Administration	Effect specificity	Author’s
SB-334867	N/l	+	P female rat 2-bottle choice	3, 10, or 30 mg/kg, i.p.	N/l	[4]
	N/l	-	P female rat Operant progressive ratio		N/l
	N/l	+	Male C57BL/6 mice Binge drinking		-

SB-334867	+	+	All procedures 15%EtOH Male C57BL/6 mice Binge drinking 20%EtOH	5 mg/kg, i.p.	N/l	[48]

SB-334867	N/l	+	Male P rat Operant progressive ratio 10%EtOH	3 μg VTA	+	[61]

SB-334867	N/l	+	Female P rat Operant progressive ratio for EtOH->PSR ->Relapse ->SB administration>PSR ->Relapse 15%EtOH	10 or 20 mg/kg, i.p.	N/l	[59]

SB-334867	+	+	Male P rat Operant progressive ratio 10%EtOH	5 or 10 mg/kg i.p.	+	[57]

SB-334867	+	+	Male C57BL/6 mice 2-bottle choice 15%EtOH	0.3, 1, 3 or 10 mg/kg i.p.	+	[49]

SB-334867	+	mNAsh + mPFC +	Male C57BL/6 mice Binge drinking 15%EtOH	3 μg mNAsh and mPFC	+	[50]
		+	Male Long Evans rat Operant progressive ratio 20%EtOH		N/l

SB-334867	+	+	Male P rat Operant responding ratio 10%EtOH	20 mg/kg, i.p.	+	[58]

GSK1059865	+	+	Male C57BL/6 mice intermittent ethanol or air exposure in inhalation chambers 15%EtOH	10, 25, 50 mg/kg i.p	+	[60]

SB-334867	N/l	+	Male Wistar rat 2-bottle choice 10%EtOH	3 ng, 6 ng NAcc	-	[44]

SB-334867	N/l	+	Male Sprague Dawley rat 2-bottle choice 10%EtOH	30 mg/kg, i.p.	+	[46]

SB-334867	N/l	+	Male Sprague-Dawley rat Operant progressive ratio cue-induced reinstatement	10, or 20 mg/kg i.p.	+	[47]
		+	20%EtOH

SB-334867	+	+	Male C57BL/6 mice Binge drinking 20%EtOH	5 or 10 mg/kg, i.p.	-	[51]

SB-334867	+	+	Male C57BL/6 mice Binge drinking 20%EtOH	6.0 pg VTA and CeA	+	[55]

SB-334867	-	+	Male Long-Evans rat Operant progressive ratio 10%EtOH	5, 10, 15, 20 mg/kg, i.p.	+	[43]

SB-408124	+	-	Male DBA/2 mice CPP	3, 10, 30 mg/kg, s.c.	N/l	[45]
		-	Male Wistar rat Operant progressive ratio
			All procedures 8%EtOH

SB-334867	+	-	Male DBA/2J mice CPP	10, 15, 20, 30, 40 mg/kg, i.p.	N/l	[52]
			20%EtOH

LSN2424100	N/l	-	P female rat 2-bottle choice	10 or 30 mg/kg, i.p.	N/l	[4]
	N/l	+	P female rat Operant progressive ratio	3, 10, 30 mg/kg i.p	N/l
	N/l	+	Male C57BL/6 mice Binge drinking	5, 30, 60 mg/kg i.p	-
			All procedures 15%EtOH

TCS-OX2-29	+	aPVT + pPVT-	Male Long-Evans rat 2-bottle-choice 20%EtOH	10 nmol aPVT, pPVT	aPVT + pPVT-	[42]

TCS-OX2-29	+	NAcc + NAcsh -	Male P rats cue-induced reinstatement of ethanol-seeking	100 μg or 300 μg NAcsh or NAcc	+	[56]
		+	Operant responding ratio 10%EtOH

TCS-OX2-29	+		Male C57BL/6 mice 2-bottle choice 15%EtOH	3 or 10 mg/kg i.p	N/l	[49]

TCS-OX2-29	+		Male C57BL/6 mice Binge drinking 15%EtOH	3 μg mNAsh	N/l	[50]
		-	Operant progressive ratio 20%EtOH		N/l

TCS-OX2-29	+		Male C57BL/6 mice Binge drinking 20%EtOH	5.0, or 7.5 μg VTA, CeA	-	[55]

JNJ10397049	+	-	Male DBA/2 mice CPP	1, 3, and 10 mg/kg, s.c.	+	[45]
		+	Male Wistar rat Operant progressive ratio
			All procedures 8%EtOH

Almorexant	N/l	+	P female rat 2-bottle choice	60 or 100 mg/kg, i.p.	N/l	[4]
		+	P female rat Operant progressive ratio	10, 30, or 60 mg/kg, i.p.	N/l
		+	Male C57BL/6 mice Binge drinking	5, 50, or 100 mg/kg, i.p.	-
			All procedures 15%EtOH

Almorexant	+	VTA + SN -	Male Long-Evans rat Operant progressive ratio 20%EtOH	3, 10 and 15 mg/kg, i.p. VTA and SN	-	[62]

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Sujets de la revue:: Sciences de la vie, Biologie moléculaire, Microbiologie et virologie, Médecine, Sciences médicales de base, Immunologie

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Orexin receptor blockers: A tool for lowering alcohol intake and alcohol addictive behavior in the light of preclinical studies

Kamila Czora-Poczwardowska

Radosław Kujawski

Julia Słyńko-Krzyżostaniak

Przemysław Ł. Mikołajczak

Michał Szulc

Catégorie d'article: Review

Publié en ligne: 29 déc. 2021

Pages: 959 - 969

Reçu: 16 août 2020

Accepté: 16 avr. 2021

DOI: https://doi.org/10.2478/ahem-2021-0007

Mots clésorexins, orexin receptors, AUD, reward system, two-bottle choice model, SB-334867

© 2021 Kamila Czora-Poczwardowska., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Summary of behavioral preclinical experiments using antagonists of OXR along with a brief description of some experimental details

Mots clés
orexins, orexin receptors, AUD, reward system, two-bottle choice model, SB-334867