Yohimbine-Induced Amygdala Activation in Pathological Gamblers: A Pilot Study

Igor Elman,David Borsook,Lino Becerra,Edward George,Evelyne Tschibelu,Rinah Yamamoto

doi:10.1371/journal.pone.0031118

Igor Elman, David Borsook + Show 4 more

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https://doi.org/10.1371/journal.pone.0031118

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Abstract

Rationale and ObjectivesThere is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress.MethodsWe induced stress by injecting yohimbine (0.2–0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings.ResultsVoxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble.ConclusionsThe present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.

Highlights

As legalized gambling activities are rapidly expanding in our society so do gambling-related public health problems [1]
There is evidence that pathological gambling (PG) is associated with heightened stress responses
Diagnosis (PG and healthy subjects) was the grouping factor and Drug was the within-subjects factor. This analysis of variance (ANOVA) resulted in a significant drug effect (F = 5.83; df = 1; p,0.05) but no significant group effect (F = 0.25; df = 1; p = 0.63) or drug by group interaction (F = 0.53; df = 1,7; p = 0.49)

Summary

Introduction

As legalized gambling activities are rapidly expanding in our society so do gambling-related public health problems [1]. The overall lifetime prevalence of problem and/or pathological gambling (PG) in the general adult population is about 5% [2,3] and its annual cost to the American society as a result of crime, decreased productivity and bankruptcies approximates $54 billion [4]. These figures likely underestimate the problems associated with PG because this is a more ‘silent’ addiction without characteristic symptoms of intoxication, needles’ marks, or overdose, and may only become apparent relatively late in the addiction process with the emergence of devastating and irreversible consequences, including attempted suicide in up to 24% of untreated individuals [4,5,6]. Like in drug addiction [21,22,23], stress can precipitate and exacerbate the maladaptive addictive behavior (gambling) and engagement in the addictive behavior or exposure to cues associated with maladaptive behavior (e.g., a slot machine) can lead to exaggerated or sensitized activation of the brain stress systems [20]

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