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

Rationale and Objectives: There 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. Methods: We 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. Results: Voxelwise 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

Neurological Soft Signs in Individuals with Pathological Gambling

Increased neurological soft signs (NSSs) have been found in a number of neuropsychiatric syndromes, including chemical addiction. The present study examined NSSs related to perceptual-motor and visuospatial processing in a behavioral addiction viz., pathological gambling (PG). As compared to mentally healthy individuals, pathological gamblers displayed significantly poorer ability to copy two- and three-dimensional figures, to recognize objects against a background noise, and to orient in space on a road-map test. Results indicated that PG is associated with subtle cerebral cortical abnormalities. Further prospective clinical research is needed to address the NSSs' origin and chronology (e.g., predate or follow the development of PG) as well as their response to therapeutic interventions and/or their ability to predict such a response

Individual clusters of amygdala activation in pathological gamblers (corrected p<0.001).

<p>The coordinates are taken from the MNI Brain Atlas. The origin of the coordinates refers to the anterior commissure.</p

phMRI of Yohimbine.

<p><b>Top: Yohimbine Infusion Procedure.</b> Following a 5 min baseline, yohimbine was infused in four separate infusions, each infusion lasting 20 sec, and with an interinfusion interval of 2 min, as shown in the box (see Text). <b>Middle: Plasma levels of Yohimbine.</b> Based on prior reports <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031118#pone.0031118-Guthrie1" target="_blank">[77]</a> doses of yohimbine reach maximal levels immediately after intravenous infusion and remain high for at least 20 min. <b>Bottom:</b> Plasma levels of norepinephrine rapidly follow yohimbine infusions <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031118#pone.0031118-Guthrie2" target="_blank">[78]</a>. These levels also remain high for the duration of the phMRI data acquisition.</p

Group medians and mean (±SDs) for the performance indices on the Copy Figure, Detection and Recognition of an Object and the Road Map tests.

<p>Group medians and mean (±SDs) for the performance indices on the Copy Figure, Detection and Recognition of an Object and the Road Map tests.</p

Detection and Recognition of an Object Test (DROT).

<p>“High noise” and “low noise” sets were presented separately, with the latter following the former. Subjects were instructed to identify the object embedded in the noise.</p

The Money Road Map Test (RMT).

<p>The continuous dotted line represents the path followed by the researcher's pen. Subjects were asked at each successive turn to indicate whether it was right or left. The smaller dotted line in the lower right serves as a practice trial.</p

The two-dimensional (diamond and cross) and three-dimensional (Necker cube, smoking pipe, hidden line elimination cube, pyramid and dissected pyramid) figures copied by the subjects (Panel A). Examples of PG subjects' performance on the Copy Figure Test (Panel B).

<p>The two-dimensional (diamond and cross) and three-dimensional (Necker cube, smoking pipe, hidden line elimination cube, pyramid and dissected pyramid) figures copied by the subjects (Panel A). Examples of PG subjects' performance on the Copy Figure Test (Panel B).</p