Yohimbine-induced amygdala activation in pathological gamblers: a pilot study.
OBJECTIVE
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.


CONCLUSIONS
The present data support the hypothesis of brain sensitization to pharmacologically-induced stress in PG.
Bedford Veterans Administration Medical Center and Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Somerville, Massachusetts, United States of America. ielman@cha.harvard.edu
Igor
I
Elman
Lino
L
Becerra
Evelyne
E
Tschibelu
Rinah
R
Yamamoto
Edward
E
George
David
D
Borsook
D058669:Adrenergic alpha-2 Receptor Antagonists; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D016739:Behavior, Addictive; D001931:Brain Mapping; D016022:Case-Control Studies; D005715:Gambling / Q000139:chemically induced / Q000209:etiology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D010865:Pilot Projects; D013312:Stress, Physiological; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine