Dataset Information

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

ABSTRACT: 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. Alcohol-dependent 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 hybridization, receptor autoradiography ([125I]OVTA binding), and immunohistochemistry. Alcohol self-administration and cue-induced reinstatement behavior was measured after intracerebroventricular 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 validation showed that oxytocin reduced cue-induced reinstatement response in dependent rats-an effect that was not observed in non-dependent 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 positively affect treatment outcomes in alcoholics.

SUBMITTER: Hansson AC

PROVIDER: S-EPMC5916348 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Hansson Anita C AC Koopmann Anne A Uhrig Stefanie S Bühler Sina S Domi Esi E Kiessling Eva E Ciccocioppo Roberto R Froemke Robert C RC Grinevich Valery V Kiefer Falk F Sommer Wolfgang H WH Vollstädt-Klein Sabine S Spanagel Rainer R

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20171101 6

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. Alcohol-dependent 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 hybridization, receptor autoradiography ([<sup>125</sup>I]OVTA bi ...[more]

PMID: 29090683

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Project description:RATIONALE:Compared to the general population, adult Attention-Deficit / Hyperactivity Disorder (ADHD) is more prevalent in patients with Alcohol Use Disorder (AUD). Impaired behavioral inhibition is a common characteristic in both ADHD and AUD. Relapse risk is increased in patients with AUD and comorbid, untreated ADHD and in AUD patients with increased neural cue-reactivity. OBJECTIVES:In this study, we examined the interaction between neural correlates of behavioral inhibition and alcohol cue-reactivity with a hybrid imaging task. METHODS:Out of 69 adult study participants, we included n?=?49 in our final analyses: Individuals had a diagnosis of either AUD (n?=?13), ADHD (n?=?14) or both (n?=?5), or were healthy controls (HC; n?=?17). The functional magnetic resonance imaging paradigm aimed to examine the combined effects of both an interference-inhibition task ("Simon-task") and an alcohol cue-reactivity task. Instead of segregating by diagnostic group, we pursued a dimensional approach in which we compared measures of AUD and ADHD severity, as well as the interaction of both, using multiple regression analyses. RESULTS:The four groups did not differ on the behavioral level on either the inhibition task or the alcohol cue-reactivity task. However, brain activation in frontal control and reward-related regions during completion of the combined tasks were related to ADHD and AUD severity (symptom load). During presentation of both alcohol cues and the inhibition task, participants with higher AUD and ADHD symptom load exhibited greater BOLD (blood oxygen level dependent) responses in subcortical reward-related regions. CONCLUSIONS:Our findings support the hypothesis that ADHD additionally diminishes inhibition ability in individuals with AUD. This may increase relapse risk when confronted with alcohol cues. Further, it is crucial for patients with comorbid AUD and ADHD to take into account not only reduced cognitive control over behavioral inhibition but also simultaneously heightened alcohol cue-reactivity.

Dataset Information

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

Publications

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

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