Dopamine mediates a directionally opposite correlation between empathy and the reinforcing effects of amphetamine and gambling in people with gambling disorder vs. healthy controls.

Understanding the relationship between empathy, subjective effects of addictive reinforcers and dopamine function in people with gambling disorder (PGD) vs. healthy controls (HCs) may inform GD treatment. The current investigation addressed this issue via retrospective analysis of data from three studies using amphetamine and a slot machine (SLOTS) as reinforcers in PGD and HCs.

Automating Detection of Drug-Related Harms on Social Media: Machine Learning Framework.

Background: A hallmark of unregulated drug markets is their unpredictability and constant evolution with newly introduced substances. People who use drugs and the public health workforce are often unaware of the appearance of new drugs on the unregulated market and their type, safe dosage, and potential adverse effects. This increases risks to people who use drugs, including the risk of unknown consumption and unintentional drug poisoning.

Towards cross-Canada monitoring of the unregulated street drug supply.

Background: The well-being of people who use drugs (PWUD) continues to be threatened by substances of unknown type or quantity in the unregulated street drug supply. Current efforts to monitor the drug supply are limited in population reach and comparability. This restricts capacity to identify and develop measures that safeguard the health of PWUD.

Corticotropin-releasing hormone and dopamine release in healthy individuals.

Corticotropin-releasing hormone (CRH) is a key component of the neuroendocrine response to stress. In animal models, CRH has been shown to modulate dopamine release, and this interaction is believed to contribute to stress-induced relapse in neuropsychiatric disorders. Here we investigated whether CRH administration induces dopamine release in humans, using positron emission tomography (PET).

Heightened Dopaminergic Response to Amphetamine at the D Dopamine Receptor in Methamphetamine Users.

Neuroimaging studies in stimulant use (eg, cocaine, methamphetamine) disorders show that diminished dopamine release by dopamine-elevating drugs is a potential marker of relapse and suggest that increasing dopamine at the D receptors may be therapeutically beneficial. In contrast, recent investigations indicate heightened D receptor levels in stimulant users prompting the view that D antagonism may help prevent relapse. Here we tested whether a 'blunted' response to amphetamine in methamphetamine (MA) users extends to D-rich brain areas.

Fatty Acid Amide Hydrolase Binding in Brain of Cannabis Users: Imaging With the Novel Radiotracer [C]CURB.

Background: One of the major mechanisms for terminating the actions of the endocannabinoid anandamide is hydrolysis by fatty acid amide hydrolase (FAAH), and inhibitors of the enzyme were suggested as potential treatment for human cannabis dependence. However, the status of brain FAAH in cannabis use disorder is unknown.

Methods: Brain FAAH binding was measured with positron emission tomography and [C]CURB in 22 healthy control subjects and ten chronic cannabis users during early abstinence.

Emotion dysregulation and amygdala dopamine D2-type receptor availability in methamphetamine users.

Background: Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM-IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala.

D3 dopamine receptor-preferring [11C]PHNO PET imaging in Parkinson patients with dyskinesia.

Objective: To investigate whether levodopa-induced dyskinesias (LID) are associated with D3 overexpression in levodopa-treated humans with Parkinson disease (PD).

Methods: In this case-control study, we used PET with the D3-preferring radioligand [(11)C]-(+)-PHNO to estimate D2/3 receptor binding in patients with levodopa-treated PD with LID (n = 12) and without LID (n = 12), and healthy control subjects matched for age, sex, education, and mental status (n = 18).

Results: Compared to nondyskinetic patients, those with LID showed heightened [(11)C]-(+)-PHNO binding in the D3-rich globus pallidus.

Relationship of Alexithymia Ratings to Dopamine D2-type Receptors in Anterior Cingulate and Insula of Healthy Control Subjects but Not Methamphetamine-Dependent Individuals.

Background: Individuals with substance-use disorders exhibit emotional problems, including deficits in emotion recognition and processing, and this class of disorders also has been linked to deficits in dopaminergic markers in the brain. Because associations between these phenomena have not been explored, we compared a group of recently abstinent methamphetamine-dependent individuals (n=23) with a healthy-control group (n=17) on dopamine D2-type receptor availability, measured using positron emission tomography with [(18)F]fallypride.

Methods: The anterior cingulate and anterior insular cortices were selected as the brain regions of interest, because they receive dopaminergic innervation and are thought to be involved in emotion awareness and processing.

Personality disorder symptomatology is associated with anomalies in striatal and prefrontal morphology.

Personality disorder symptomatology (PD-Sx) can result in personal distress and impaired interpersonal functioning, even in the absence of a clinical diagnosis, and is frequently comorbid with psychiatric disorders such as substance use, mood, and anxiety disorders; however, they often remain untreated, and are not taken into account in clinical studies. To investigate brain morphological correlates of PD-Sx, we measured subcortical volume and shape, and cortical thickness/surface area, based on structural magnetic resonance images. We investigated 37 subjects who reported PD-Sx exceeding DSM-IV Axis-II screening thresholds, and 35 age, sex, and smoking status-matched control subjects.

Differential cardiovascular and hypothalamic pituitary response to amphetamine in male pathological gamblers versus healthy controls.

Cardiovascular and hypothalamic pituitary axis (HPA) disturbances have been observed in individuals who are pathological gamblers (PGs). These may partly derive from chronic exposure to gambling. Response to amphetamine (AMPH) may reveal such disturbances while controlling for differential conditioned responses to gambling in PGs vs healthy controls (HCs).

Imaging the D3 dopamine receptor across behavioral and drug addictions: Positron emission tomography studies with [(11)C]-(+)-PHNO.

Chronic drug use has been associated with dopaminergic abnormalities, detectable in humans with positron emission tomography (PET). Among these, a hallmark feature is low D2 dopamine receptor availability, which has been linked to clinical outcomes, but has not yet translated into a therapeutic strategy. The D3 dopamine receptor on the other hand has gained increasing attention, as, in contrast to D2, chronic exposure to drugs has been shown to up-regulate this receptor subtype in preclinical models of addiction-a phenomenon linked to dopamine system sensitization and drug-seeking.

Occupancy of Dopamine D3 and D2 Receptors by Buspirone: A [11C]-(+)-PHNO PET Study in Humans.

There is considerable interest in blocking the dopamine D3 receptor (DRD3) versus the D2 receptor (DRD2) to treat drug addiction. However, there are currently no selective DRD3 antagonists available in the clinic. The anxiolytic drug buspirone has been proposed as a potential strategy as findings suggest that this drug has high in vitro affinity for DRD3, binds to DRD3 in brain of living non-human primate, and also disrupts psychostimulant self-administration in preclinical models.

[¹¹C]-(+)-PHNO PET imaging of dopamine D(2/3) receptors in Parkinson's disease with impulse control disorders.

Dopamine agonist medications with high affinity for the D3 dopamine receptor are commonly used to treat Parkinson's disease, and have been associated with pathological behaviors categorized under the umbrella of impulse control disorders (ICD). The aim of this study was to investigate whether ICD in Parkinson's patients are associated with greater D3 dopamine receptor availability. We used positron emission tomography (PET) radioligand imaging with the D3 dopamine receptor preferring agonist [¹¹C]-(+)-propyl-hexahydro-naphtho-oxazin (PHNO) in Parkinson's patients with (n = 11) and without (n = 21) ICD, and age-, sex-, and education-matched healthy control subjects (n = 18).

Measuring cigarette smoking-induced cortical dopamine release: A [¹¹C]FLB-457 PET study.

Striatal dopamine (DA) is thought to have a fundamental role in the reinforcing effects of tobacco smoking and nicotine. Microdialysis studies indicate that nicotine also increases DA in extrastriatal brain areas, but much less is known about its role in addiction. High-affinity D2/3 receptor radiotracers permit the measurement of cortical DA in humans using positron emission tomography (PET).

Pathological choice: the neuroscience of gambling and gambling addiction.

Gambling is pertinent to neuroscience research for at least two reasons. First, gambling is a naturalistic and pervasive example of risky decision making, and thus gambling games can provide a paradigm for the investigation of human choice behavior and "irrationality." Second, excessive gambling involvement (i.

What is the role of the D3 receptor in addiction? A mini review of PET studies with [(11)C]-(+)-PHNO.

The chronic use of drugs, including psychostimulants such as cocaine and amphetamine, has been associated with low D2/3 dopamine receptor availability, which in turn has been linked to poor clinical outcome. In contrast, recent studies focused on the D3 receptor (a member of the D2-like receptor family) suggest that chronic exposure to stimulant drugs can up-regulate this receptor subtype, which, in preclinical models, is linked to dopamine system sensitization - a process hypothesized to contribute to relapse in addiction. In this mini review we present recent human data suggesting that the D3 receptor may contribute to core features of addiction, and discuss the usefulness of the PET imaging probe [(11)C]-(+)-PHNO in investigating this question.

Heightened D3 dopamine receptor levels in cocaine dependence and contributions to the addiction behavioral phenotype: a positron emission tomography study with [11C]-+-PHNO.

The dopamine system is a primary treatment target for cocaine dependence (CD), but research on dopaminergic abnormalities (eg, D2 receptor system deficiencies) has so far failed to translate into effective treatment strategies. The D3 receptor system has recently attracted considerable clinical interest, and D3 antagonism is now under investigation as a novel avenue for addiction treatment. The objective here was to evaluate the status and behavioral relevance of the D3 receptor system in CD, using the positron emission tomography (PET) radiotracer [(11)C]-(+)-PHNO.

Overlapping neural substrates between intentional and incidental down-regulation of negative emotions.

Emotion regulation can be achieved in various ways, but few studies have evaluated the extent to which the neurocognitive substrates of these distinct operations overlap. In the study reported here, functional magnetic resonance imaging (fMRI) was used to measure activity in the amygdala and prefrontal cortex of 10 participants who completed two independent tasks of emotion regulation-reappraisal, measuring intentional emotion regulation, and affect labeling, measuring incidental emotion regulation-with the objective of identifying potential overlap in the neural substrates underlying each task. Analyses focused on a priori regions of interest in the amygdala and inferior frontal gyrus (IFG).

Neural correlates of affect processing and aggression in methamphetamine dependence.

Context: Methamphetamine abuse is associated with high rates of aggression but few studies have addressed the contributing neurobiological factors.

Objective: To quantify aggression, investigate function in the amygdala and prefrontal cortex, and assess relationships between brain function and behavior in methamphetamine-dependent individuals.

Design: In a case-control study, aggression and brain activation were compared between methamphetamine-dependent and control participants.

Smoking reduces conflict-related anterior cingulate activity in abstinent cigarette smokers performing a Stroop task.

Prior research suggests that abrupt initiation of abstinence from cigarette smoking reduces neural cognitive efficiency. When cognitive efficiency is high, processing speed and accuracy are maximized with minimal allocation of cognitive resources. The study presented here tested the effects of resumption of smoking on cognitive response conflict after overnight abstinence from smoking, hypothesizing that smoking would enhance cognitive efficiency.