Martin Zack

Development and psychometric evaluation of a three-dimensional Gambling Motives Questionnaire

AIMS This study was designed to develop and evaluate a self-report measure of gambling motives. Participants A community-recruited sample of 193 gamblers (70% male; mean age = 35.5 years) were selected to fill two groups according to scores on the South Oaks Gambling Screen: probable pathological gamblers (PPG; n = 154) and non-pathological gamblers (NPG; n = 39). MEASURES Participants completed a novel 15-item measure of gambling motives called the Gambling Motives Questionnaire (GMQ), which was modeled after the original Drinking Motives Questionnaire, as well as a variety of gambling behavior and problem criterion measures. RESULTS An exploratory principal components analysis revealed three intercorrelated factors tapping enhancement (ENH), coping (COP), and social (SOC) motives, respectively. Each GMQ subscale showed good internal consistency (alphas > 0.80). The PPG group scored higher on all three scales than the NPG group, with larger differences for ENH and COP. In line with the clinical literature, PPG women scored higher than PPG men on the COP subscale but also, unexpectedly, on the SOC subscale. In concurrent validity analyses, ENH consistently predicted greater gambling behavior, and COP and ENH consistently predicted more severe gambling problems. With gambling behavior levels controlled, only COP remained a significant predictor of gambling problem severity. Finally, gender interacted with gambling motives in predicting gambling problem severity: COP predicted gambling problems more strongly in women, whereas ENH predicted gambling problems more strongly in men. CONCLUSIONS The GMQ appears to be a promising tool for both research and clinical applications with problem gamblers.

Higher Binding of the Dopamine D3 Receptor-Preferring Ligand [11C]-(+)-Propyl-Hexahydro-Naphtho-Oxazin in Methamphetamine Polydrug Users: A Positron Emission Tomography Study

Positron emission tomography (PET) findings suggesting lower D2-type dopamine receptors and dopamine concentration in brains of stimulant users have prompted speculation that increasing dopamine signaling might help in drug treatment. However, this strategy needs to consider the possibility, based on animal and postmortem human data, that dopaminergic activity at the related D3 receptor might, in contrast, be elevated and thereby contribute to drug-taking behavior. We tested the hypothesis that D3 receptor binding is above normal in methamphetamine (MA) polydrug users, using PET and the D3-preferring ligand [11C]-(+)-propyl-hexahydro-naphtho-oxazin ([11C]-(+)-PHNO). Sixteen control subjects and 16 polydrug users reporting MA as their primary drug of abuse underwent PET scanning after [11C]-(+)-PHNO. Compared with control subjects, drug users had higher [11C]-(+)-PHNO binding in the D3-rich midbrain substantia nigra (SN; +46%; p < 0.02) and in the globus pallidus (+9%; p = 0.06) and ventral pallidum (+11%; p = 0.1), whereas binding was slightly lower in the D2-rich dorsal striatum (approximately −4%, NS; −12% in heavy users, p = 0.01) and related to drug-use severity. The [11C]-(+)-PHNO binding ratio in D3-rich SN versus D2-rich dorsal striatum was 55% higher in MA users (p = 0.004), with heavy but not moderate users having ratios significantly different from controls. [11C]-(+)-PHNO binding in SN was related to self-reported “drug wanting.” We conclude that the dopamine D3 receptor, unlike the D2 receptor, might be upregulated in brains of MA polydrug users, although lower dopamine levels in MA users could have contributed to the finding. Pharmacological studies are needed to establish whether normalization of D3 receptor function could reduce vulnerability to relapse in stimulant abuse.

Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers

Previous research suggests that gambling can induce effects that closely resemble a psychostimulant drug effect. Modest doses of addictive drugs can prime motivation for drugs with similar properties. Together, these findings imply that a dose of a psychostimulant drug could prime motivation to gamble in problem gamblers. This study assessed priming effects of oral D-amphetamine (AMPH) (30 mg) in a within-subject, counter-balanced, placebo-controlled design in problem gamblers (n=10), comorbid gamblerdrinkers (n=6), problem drinkers (n=8), and healthy controls (n=12). Modified visual analog scales assessed addictive motivation and subjective effects. A modified rapid reading task assessed pharmacological activation of words from motivationally relevant and irrelevant semantic domains (Gambling, Alcohol, Positive Affect, Negative Affect, Neutral). AMPH increased self-reported motivation for gambling in problem gamblers. Severity of problem gambling predicted positive subjective effects of AMPH and motivation to gamble under the drug. There was little evidence that AMPH directly primed motivation for alcohol in problem drinkers. On the reading task, AMPH produced undifferentiated improvement in reading speed to all word classes in Nongamblers. By contrast, in the two problem gambler groups, AMPH improved reading speed to Gambling words while profoundly slowing reading speed to motivationally irrelevant Neutral words. The latter finding was interpreted as directly congruent with models, which contend that priming of addictive motivation involves a linked suppression of motivationally irrelevant stimuli. This study provides experimental evidence that psychostimulant-like neurochemical activation is an important component of gambling addiction.

Subtyping Pathological Gamblers on the Basis of Affective Motivations for Gambling: Relations to Gambling Problems, Drinking Problems, and Affective Motivations for Drinking

Pathological gamblers who drink when gambling (n=158; 77% men; mean age=36.0 years) completed the Inventory of Gambling Situations (IGS) and gambling and drinking criterion measures. Principal components analysis on the IGS subscales revealed negative (e.g., Unpleasant Emotions) and positive (e.g., Pleasant Emotions) gambling situation factors. Subjecting IGS factor scores to cluster analysis revealed three clusters: (a) enhancement gamblers, with low negative and high positive factor scores; (b) coping gamblers, with very high negative and high positive factor scores; and (c) low emotion regulation gamblers, with low negative and positive factor scores (59%, 23%, and 18% of the sample, respectively). Clusters were validated with a direct measure of gambling motives. Additional validity analyses showed that coping gamblers scored higher than the other groups on a variety of different gambling activities, gambling problems, drinking frequency, drinking problems, and coping drinking motives, whereas low emotion regulation gamblers scored lower than the other groups on gambling frequency, gambling problems, drinking quantity, and enhancement drinking motives. The findings validate this empirical approach to subtyping gamblers and suggest consistency of motives across addictive behaviors.

The D2/3 dopamine receptor in pathological gambling: a positron emission tomography study with [11C]‐(+)‐propyl‐hexahydro‐naphtho‐oxazin and [11C]raclopride

AIMS Pathological gambling (PG) shares diagnostic features with substance use disorder (SUD), but the neurochemical mechanisms underlying PG are poorly understood. Because dopamine (DA), a neurotransmitter implicated in reward and reinforcement, is probably involved, we used positron emission tomography (PET) to test whether PG is associated with abnormalities in D2 and D3 receptor levels, as observed in SUD. DESIGN Case-control study comparing PG to healthy control (HC) subjects. SETTING Academic research imaging centre. PARTICIPANTS Thirteen non-treatment-seeking males meeting DSM-IV criteria for PG, and 12 matched HC (11 of whom completed PET). MEASUREMENTS Two PET scans (one with the D3 receptor preferring agonist [11C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) and the other with [11C]raclopride) to assess D(2/3) DA receptor availability, and behavioural measures (self-report questionnaires and slot-machine game) to assess subjective effects and relationships to PET measures. FINDINGS Binding of both radiotracers did not differ between groups in striatum or substantia nigra (SN) (all P > 0.1). Across PG, [11C]-(+)-PHNO binding in SN, where the signal is attributable primarily to D3 receptors, correlated with gambling severity (r = 0.57, P = 0.04) and impulsiveness (r = 0.65, P = 0.03). In HC, [11C]raclopride binding in dorsal striatum correlated inversely with subjective effects of gambling (r = -0.70, P = 0.03) and impulsiveness (r = -0.70, P = 0.03). CONCLUSIONS Unlike with substance use disorder, there appear to be no marked differences in D2 /D3 levels between healthy subjects and pathological gamblers, suggesting that low receptor availability may not be a necessary feature of addiction. However, relationships between [11C]-(+)-PHNO binding and gambling severity/impulsiveness suggests involvement of the D3 receptor in impulsive/compulsive behaviours.

A D2 Antagonist Enhances the Rewarding and Priming Effects of a Gambling Episode in Pathological Gamblers

Previous research indicated shared neurochemical substrates for gambling and psychostimulant reward. This suggests that dopamine substrates may directly govern the reinforcement process in pathological gambling. To investigate this issue, the present study assessed the effects of the relatively selective dopamine D2 antagonist, haloperidol (3 mg, oral) on responses to actual gambling (15 min on a slot machine) in 20 non-comorbid pathological gamblers and 18 non-gambler controls in a placebo-controlled, double-blind, counterbalanced design. In gamblers, haloperidol significantly increased self-reported rewarding effects of gambling, post-game priming of desire to gamble, facilitation of reading speed to Gambling words, and gambling-induced elevation in blood pressure. In controls, haloperidol augmented gambling-induced elevation in blood pressure, but had no effect on other indices. The findings provide direct experimental evidence that the D2 substrate modulates gambling reinforcement in pathological gamblers.

Effects of abstinence and smoking on information processing in adolescent smokers

Abstract. Rationale: Although adolescent smokers appear to display some of the hallmark features of dependence, the biological and behavioral effects of smoking in this population are poorly understood. Objectives: This study aimed to define empirically the effects of abstinence and smoking in adolescent smokers, using indices validated in adult smokers. Methods: Subjects were 16 young novice smokers (five male, 11 female), ages 14–18 years. A modified Stroop task measured the ability to inhibit attention to smoking-related cues; the classic Stroop task measured the ability to inhibit a pre-potent response (i.e. reading a word); a rapid information processing (RIP) task measured vigilance. Results: Abstinence increased and smoking decreased the intrusiveness of smoking cues. Parallel effects were seen in commission errors on the RIP task. These effects were restricted to heavier smokers (>11 cigarettes/day). Subjective withdrawal effects predicted the intrusiveness of smoking words during abstinence. The number of cigarettes smoked per day predicted the beneficial effect of smoking on the classic as well as modified Stroop tasks. The physiological effects of abstinence and smoking predicted RIP performance. Conclusions: Abstinence impairs and smoking improves inhibitory information processing in young novice smokers in a manner similar to adult smokers. Daily frequency of smoking is a critical moderator of these effects.

In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [ 11 C]-(+)-PHNO

Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [11C]-(+)-PHNO during a dual-scan protocol to investigate DA release in response to oral amphetamine in pathological gamblers (n=12) and healthy controls (n=11). In contrast with human neuroimaging findings in drug addiction, we report the first evidence that PG is associated with greater DA release in dorsal striatum (54–63% greater [11C]-(+)-PHNO displacement) than controls. Importantly, dopaminergic response to amphetamine in gamblers was positively predicted by D3 receptor levels (measured in substantia nigra), and related to gambling severity, allowing for construction of a mechanistic model that could help explain DA contributions to PG. Our results are consistent with a hyperdopaminergic state in PG, and support the hypothesis that dopaminergic sensitization involving D3-related mechanisms might contribute to the pathophysiology of behavioral addictions.

Effects of the atypical stimulant modafinil on a brief gambling episode in pathological gamblers with high vs. low impulsivity

Abstract Pathological gambling (PG) is a serious psychiatric disorder afflicting 1-3% of the general population. Experimental evidence indicates shared neurochemical substrates for PG and psychostimulant addiction. Impulsivity characterizes one key subtype of PG. Therefore, medications that ameliorate psychostimulant addiction and impulsive syndromes might also benefit impulsive PG subjects. The atypical stimulant, modafinil reduces cocaine abuse and impulsivity in patients with ADHD. The present study sought to determine if modafinil (200 mg) would reduce the reinforcing effects of slot machine gambling in PG subjects, and if this effect was stronger in high (H-I) vs. low (L-I) impulsivity subjects (N = 20). A placebo-controlled, double-blind, counterbalanced, repeated measures design was employed. Apart from bet size, which declined uniformly in both groups under drug, modafinil had bi-directional effects in the two groups. In H-I subjects, the drug decreased desire to gamble, salience of Gambling words, disinhibition and risky decision-making. In L-I subjects, modafinil increased scores on these indices. Modafinil also differentially affected blood pressure response to the game in the two groups. These findings for modafinil appear to fit well with a growing literature demonstrating bi-directional effects of D2 agonists as a function of trait impulsivity. Impulsivity could critically moderate medication response in PG.

Parallel roles for dopamine in pathological gambling and psychostimulant addiction.

A variety of evidence suggests important commonalities in the neurochemical basis of reinforcement in pathological gambling (PG) and psychostimulant addiction. This article focuses on the parallel and specific roles that dopamine (DA) activation plays in these two disorders, beyond its generic role in reinforcement. A psychostimulant-mimetic model for PG is proposed based on evidence from the following domains: Acute subjective-behavioral effects of gambling and psychostimulants; Effects of anticipated rewards and uncertainty of reward delivery (key elements of gambling) on DA release; Relationship between DA release and positive arousal; Cross-priming of motivation for gambling by amphetamine; Effects of DA D2 antagonists on gambling and amphetamine reward; Effects of mixed D1-D2 antagonists on clinical symptoms of PG; Effects of DA D2 agonists on experimental measures of risk-taking, gambling, and induction of PG in patients with Parkinsons disease; Electrophysiological and cognitive disturbances associated with chronic exposure to gambling and psychostimulants, and the possible role of sensitization in these effects. Limitations of the model regarding the exclusive role of DA are discussed with particular reference to genetic risk, co-morbidity, and sub-types of PG. Suggestions for future research include isolating the roles of DA receptor subtypes in PG, and parallel within-subject assessment of DA manipulations on gambling and psychostimulant reinforcement in PG subjects and controls.