Increased Occupancy of Dopamine Receptors in Human Striatum during Cue-Elicited Cocaine Craving

Striatal dopamine (DA) is increased by virtually all drugs of abuse, including alcohol. However, drug-associated cues are also known to provoke striatal DA transmission-a phenomenon linked to the motivated behaviors associated with addiction. To our knowledge, no one has tested if alcohol's classically conditioned flavor cues, in the absence of a significant pharmacologic effect, are capable of eliciting striatal DA release in humans. Employing positron emission tomography (PET), we hypothesized that beer's flavor alone can reduce the binding potential (BP) of [ 11 C]raclopride (RAC; a reflection of striatal DA release) in the ventral striatum, relative to an appetitive flavor control. Forty-nine men, ranging from social to heavy drinking, mean age 25, with a varied family history of alcoholism underwent two [ 11 C]RAC PET scans: one while tasting beer, and one while tasting Gatorade. Relative to the control flavor of Gatorade, beer flavor significantly increased self-reported desire to drink, and reduced [ 11 C]RAC BP, indicating that the alcohol-associated flavor cues induced DA release. BP reductions were strongest in subjects with first-degree alcoholic relatives. These results demonstrate that alcoholconditioned flavor cues can provoke ventral striatal DA release, absent significant pharmacologic effects, and that the response is strongest in subjects with a greater genetic risk for alcoholism. Striatal DA responses to salient alcohol cues may thus be an inherited risk factor for alcoholism.

Section: Discussioncontrasting

confidence: 56%

Beer Flavor Provokes Striatal Dopamine Release in Male Drinkers: Mediation by Family History of Alcoholism

Oberlin

Džemidžić

Tran

et al. 2013

“…These findings suggest that both midbrain and VS responses during anticipatory processing may represent biomarkers for approach motivation relating to abstinence in CD. Although previous studies demonstrate striatal dopamine surges following drug-cue exposure in CD that positively correlate with craving measures (Boileau et al, 2007;Volkow et al, 2006;Wong et al, 2006), here we show that individual changes in non-drug anticipatory responsivity in the striatum relate to abstinence. The current study demonstrates abstinence-related neurofunctional changes during recovery, particularly relating to incentive salience signal readjustments linked to measures of reduced cocaine use over time.…”

Section: Discussionmentioning

confidence: 54%

Neurofunctional Reward Processing Changes in Cocaine Dependence During Recovery

Balodis

Kober

Worhunsky

et al. 2016

Although reward processing appears altered in addiction, few studies track neurofunctional changes following treatment or relate these to measures of reduced drug use. The current study examined neurofunctional alterations in reward processing in cocaine dependence (CD) pretreatment and posttreatment to determine whether these changes relate to clinically meaningful outcome indicators. Treatmentseeking CD outpatients (N = 29) underwent functional magnetic resonance imaging while performing a monetary incentive delay task (MIDT) pretreatment and posttreatment. The MIDT parses anticipatory from outcome phases of reward/loss processing. Abstinence indicators (negative urines, days abstinent from cocaine during follow-up) were collected throughout treatment and up to 1 year later. Healthy control (HC) participants (N = 28) were also scanned twice with the MIDT. Relative to pretreatment, at posttreatment CD participants demonstrated increased anticipatory reward activity in the midbrain, thalamus, and precuneus (p FWE o0.05). Increased midbrain activity correlated with cocaine abstinence during the 1-year follow-up. Ventral striatal (VS) activity during loss anticipation correlated negatively with negative urine screens. HC group test-retest results showed decreased ventromedial prefrontal cortex activity during winning outcomes. CD-HC group-by-time differences revealed increased left inferior frontal gyrus activity in the CD group during anticipatory phases at posttreatment. In CD participants, increased posttreatment activity in dopamine-innervated regions suggests lowered thresholds in anticipatory signaling for non-drug rewards. Midbrain and VS responses may represent biomarkers associated with CD abstinence. Abstinence-related neurobiological changes occur in similar regions implicated during active use and may possibly be used to track progress during short-and long-term recovery.

“…However, in that study, cues were presented via audiotaped scripts. Finally, the PutFwhich makes up part of the dorsal striatumFhas Individual differences in smoking cue-reactivity FJ McClernon et al 2154 been implicated in craving for drugs including alcohol and cocaine (Heinz et al, 2005;Volkow et al, 2006;Wong et al, 2006).…”

Section: Negative Affect and Sexmentioning

confidence: 99%

Individual Differences in Nicotine Dependence, Withdrawal Symptoms, and Sex Predict Transient fMRI-BOLD Responses to Smoking Cues

McClernon

Kozink

Rose

2007

191

146

Exposure to smoking cues increases craving for cigarettes and can precipitate relapse. Whereas brain imaging studies have identified a distinct network of brain regions subserving the processing of smoking cues, little is known about the influence of individual difference factors and withdrawal symptoms on brain cue reactivity. Multiple regression analysis was used to evaluate relations between individual difference factors and withdrawal symptoms and event-related blood oxygen level-dependent responses to visual smoking cues in a sample of 30 smokers. Predictors were self-report nicotine dependence (Fagerströ m test of nicotine dependence, FTND), prescan withdrawal symptoms (craving and negative affect), and sex. The unique variance of each predictor was examined after controlling for each of the others. Positive associations were observed between FTND and reactivity to cues in right anterior cingulate and orbitofrontal cortex (OFC) whereas negative associations were observed between prescan craving and reactivity in ventral striatum. Higher negative affect or being male was associated with greater reactivity in left hippocampus and left OFC. Women exhibited greater cue reactivity than men in regions including the cuneus and left superior temporal gyrus. Individual difference factors and withdrawal symptoms were uniquely associated with brain reactivity to smoking cues in regions subserving reward, affect, attention, motivation, and memory. These findings provide further evidence that reactivity to conditioned drug cues is multiply determined and suggest that smoking cessation treatments designed to reduce cue reactivity focus on each of these variables.