Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans

被引：92

作者：

Hansson, Anita C. ^{[1
]}

Koopmann, Anne ^{[2
]}

Uhrig, Stefanie ^{[1
]}

Buhler, Sina ^{[2
]}

Domi, Esi ^{[3
,6
]}

Kiessling, Eva ^{[1
]}

Ciccocioppo, Roberto ^{[3
]}

Froemke, Robert C. ^{[4
]}

Grinevich, Valery ^{[5
]}

Kiefer, Falk ^{[2
]}

Sommer, Wolfgang H. ^{[1
,2
]}

Vollstaedt-Klein, Sabine ^{[2
]}

Spanagel, Rainer ^{[1
]}

机构：

[1] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Inst Psychopharmacol, Mannheim, Germany

[2] Heidelberg Univ, Dept Addict Behav & Addict Med, Cent Inst Mental Hlth Mannheim, Med Fac Mannheim, Mannheim, Germany

[3] Univ Camerino, Sch Pharm, Pharmacol Unit, Camerino, Italy

[4] NYU, Sch Med, Dept Otolaryngol, Skirball Inst Biomol Med,Neurosci Inst, New York, NY USA

[5] German Canc Res Ctr, Schaller Res Grp Neuropeptides, Heidelberg, Germany

[6] Linkoping Univ, Ctr Social & Affect Neurosci, Inst Clin & Expt Med, S-58183 Linkoping, Sweden

来源：

NEUROPSYCHOPHARMACOLOGY | 2018年 / 43卷 / 06期

关键词：

MEDIAL PREFRONTAL CORTEX; INTRANASAL OXYTOCIN; ETHANOL-CONSUMPTION; NEUROANATOMICAL DISTRIBUTION; PARAVENTRICULAR NUCLEUS; INDUCED REINSTATEMENT; ALLOPARENTAL CARE; SEEKING BEHAVIOR; SOCIAL COGNITION; RECEPTOR-BINDING;

D O I：

10.1038/npp.2017.257

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Approved pharmacological treatments for alcohol use disorder are limited in their effectiveness, and new drugs that can easily be translated into the clinic are warranted. One of those candidates is oxytocin because of its interaction with several alcohol-induced effects. Alcoholdependent rats as well as post-mortem brains of human alcoholics and controls were analyzed for the expression of the oxytocin system by qRT-PCR, in situ hybridizaton, receptor autoradiography ([(125)l]OVTA binding), and immunohistochemistry. Alcohol self administration and cue-induced reinstatement behavior was measured after intracerebroventicular injection of 10 nM oxytocin in dependent rats. Here we show a pronounced upregulation of oxytocin receptors in brain tissues of alcohol dependent rats and deceased alcoholics, primarily in frontal and striatal areas. This upregulation stems most likely from reduced oxytocin expression in hypothalamic nuclei. Pharmacological validaton showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in nondependent rats. Finally, a clinical pilot study (German clinical trial number DRKS00009253) using functional magnetic resonance imaging in heavy social male drinkers showed that intranasal oxytocin (24 IU) decreased neural cue-reactivity in brain networks similar to those detected in dependent rats and humans with increased oxytocin receptor expression. These studies suggest that oxytocin might be used as an anticraving medication and thus may positvely affect treatment outcomes in alcoholics.

引用

页码：1235 / 1246

页数：12

共 87 条

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