Correlation Between Dopamine D2 Receptors in the Ventral Striatum and Central Processing of Alcohol Cues and Craving

Heinz, Andreas; Siessmeier, Thomas; Wrase, Jana; Hermann, Derik; Klein, Sabine; Grüsser-Sinopoli, Sabine Miriam; Flor, Herta; Braus, Dieter F.; Buchholz, Hans Georg; Gründer, Gerhard; Schreckenberger, Mathias; Smolka, Michael N.; Rösch, Frank; Mann, Karl; Bartenstein, Peter

doi:10.1176/appi.ajp.161.10.1783

Cited by 371 publications

(277 citation statements)

References 37 publications

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“…In line with this, alcoholics with lower levels of striatal D2 receptors report greater craving and display greater cueinduced activation of the medial prefrontal cortex and anterior cingulateFbrain regions involved in motivation and attention (Heinz et al, 2004). In cocaine addicts, PET research shows that exposure to cocaine cues increases endogenous dopamine activity at D2 receptors in the dorsal striatum and the magnitude of this effect predicts craving (Volkow et al, 2006).…”

Section: Introductionmentioning

confidence: 69%

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

Zack

Poulos

2007

Neuropsychopharmacol

153

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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.

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Section: Introductionmentioning

confidence: 69%

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

Zack

Poulos

2007

Neuropsychopharmacol

153

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“…Experimental procedures have been developed to assess these processes (Eisenberg et al, 2007;Goldstein and Volkow, 2002). Addiction-related pictures and words elicit involuntary attention (Field et al, 2005;Hester et al, 2006), and activate reward-related brain circuitry in addicted individuals Heinz et al, 2004), reflecting their incentive salience. Addicted individuals also perform poorly on experimental measures of impulsivity, a tendency augmented by doses of their addictive substance (Bjork et al, 2004;Fillmore et al, 2006).…”

mentioning

confidence: 99%

Stress and Alcohol Cues Exert Conjoint Effects on Go and Stop Signal Responding in Male Problem Drinkers

Zack

Woodford

Tremblay

et al. 2010

Neuropsychopharmacol

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Stress, cues, and pharmacological priming are linked with relapse to addictive behavior. Increased salience and decreased inhibitory control are thought to mediate the effects of relapse-related stimuli. However, the functional relationship between these two processes is unclear. To address this issue, a modified Stop Signal Task was employed, which used Alcohol, Neutral, and Non-Words as Go stimuli, and lexical decision as the Go response. Subjects were 38 male problem drinkers (mean Alcohol Dependence Scale (ADS) score: 18.0). Uncontrollable noise (B10 min at 110 dB) was the stressor; nonalcoholic placebo beer (P-Beer) was the cue manipulation, and alcohol (0.7 g/kg), the pharmacological prime. Half the sample received alcohol, and half P-Beer. Stress and beverage (test drink vs soft drink) were manipulated within subjects on two sessions, with half the sample receiving active manipulations together and half receiving them separately. Go response time (RT) and Stop Signal RT (SSRT) were slower to Alcohol than Neutral words. Stress augmented this bias. Alcohol and P-Beer impaired overall SSRT. Stress impaired neither overall SSRT nor Go RT. SSRT to Neutral words and Non-Words correlated inversely with Go RT to Alcohol and Neutral words, and Non-Words. ADS correlated directly with SSRT to Alcohol words. A resource allocation account was proposed, whereby diversion of limited resources to salient cues effectively yoked otherwise independent Go and Stop processes. Disturbances of prefrontal norepinephrine and dopamine were cited as possibly accounting for these effects. Treatments that optimize prefrontal catecholamine transmission may deter relapse by reducing disinhibitory effects of salient eliciting stimuli.

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“…These data are consistent with the hypothesis that behavioral changes induced by sign-tracking procedures are related to changes in the dopamine system, and in a manner noted by addiction researchers. For example, lower levels of D2 receptor have been associated with increased craving (Heinz et al, 2004), and increased reports of "drug-liking" in humans (Volkow et al, 2002). Finally, Flagel and her associates (unpublished data) have noted that rats selectively bred for high responsivity to environmental novelty stress are almost exclusively sign-trackers in food US procedures and rats selectively bred for low responsivity to environmental novelty stress exhibit almost exclusively goal-tracking, moving to the location of the food receptacle rather than to the lever CS.…”

Section: Psychomotor Sensitizationmentioning

confidence: 99%

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

Tomie

Grimes

Pohorecky

2008

Brain Research Reviews

148

134

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Drug abuse researchers have noted striking similarities between behaviors elicited by Pavlovian signtracking procedures and prominent symptoms of drug abuse. In Pavlovian sign-tracking procedures, repeated paired presentations of a small object (conditioned stimulus, CS) with a reward (unconditioned stimulus, US) elicits a conditioned response (CR) that typically consists of approaching the CS, contacting the CS, and expressing consummatory responses at the CS. Signtracking CR performance is poorly controlled and exhibits spontaneous recovery and long-term retention, effects that resemble relapse. Sign-tracking resembles psychomotor activation, a syndrome of behavioral responses evoked by addictive drugs, and the effects of sign-tracking on corticosterone levels and activation of dopamine pathways resemble the neurobiological effects of abused drugs. Finally, the neurobiological profile of individuals susceptible to sign-tracking resembles the pathophysiological profile of vulnerability to drug abuse, and vulnerability to sign-tracking predicts vulnerability to impulsive responding and alcohol self-administration. Implications of sign-tracking for models of drug addiction are considered.

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Correlation Between Dopamine D2 Receptors in the Ventral Striatum and Central Processing of Alcohol Cues and Craving

Abstract: In alcoholics, dopaminergic dysfunction in the ventral striatum may attribute incentive salience to alcohol-associated stimuli, so that alcohol cues elicit craving and excessive activation of neural networks associated with attention and behavior control.

Cited by 371 publications

References 37 publications

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

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

Stress and Alcohol Cues Exert Conjoint Effects on Go and Stop Signal Responding in Male Problem Drinkers

Behavioral characteristics and neurobiological substrates shared by Pavlovian sign-tracking and drug abuse

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