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

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.

Evidence for GABA‐A receptor dysregulation in gambling disorder: correlation with impulsivity

“…Notably, the positive correlation with [ 11 C]Ro15‐4513 V T and NU in the amygdala remained significant after controlling for anxiety. The amygdala is a key region involved in a number of processes such as emotional processing, fear, reward valence and neuropsychiatric disorders including addiction and anxiety (Elman et al 2012; Janak and Tye 2015; van Holst et al 2012). However, evidence from neuroimaging studies using non‐specific benzodiazepine radiotracers [ 11 C]flumazenil PET or [ 123 I]iomazenil SPET about GABA A receptor availability within the amygdala in relation to these processes is limited and inconsistent.…”

Gambling Disorder and Other Behavioral Addictions

“…94 Noradrenaline may be involved in the peripheral arousal associated with gambling. 95,96 Opioid antagonists (e.g., naltrexone, nalmefene) have demonstrated superiority over placebo in multiple randomized clinical trials. 41,97,98 …”

Pain and suicidality: Insights from reward and addiction neuroscience

“…Such hypersensitive state is further amplified through the Cross-Sensitization (Elman et al, 2012; George et al, 2012; Robinson and Berridge, 2003) when prior exposure to one stimulus (e.g., drug) increases subsequent response to itself (Basso et al, 1999; Self and Nestler, 1998) and to a different stimulus (e.g., stress) and in the reversed order, enhancement of drug motivational states e.g., craving following prior stress exposure (George et al, 2012). This anti-reward loop is termed “spiraling distress cycle” (Goldstein and McEwen, 2002; Koob and Le Moal, 2001) whereby a trivial event (e.g., psychosocial stress) can mount escalating dopamine releases in the striatum causing craving and further worsening symptoms of addiction.…”

“…Such conceptualization offers structured algorithms for diagnostic, preventive and therapeutic pursuits in patients with addictive disorders. Clinical interviews and psychometric assessments may define opponent/anti-reward neuroadaptational states, while sensitization, cross-sensitization and aberrant learning could be demonstrated via neuroimaging in conjunction with cognitive and biochemical challenges procedures (Elman et al, 2005, 2009, 2012; Hopper et al, 2008). …”