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

Okita, Kyoji; Ghahremani, Dara G.; Payer, Doris; Robertson, Chelsea L.; Dean, Andy C.; Mandelkern, M.; London, Edythe D.

doi:10.1016/j.drugalcdep.2016.01.029

Cited by 25 publications

(25 citation statements)

References 70 publications

(79 reference statements)

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“…Using PET techniques, widespread dopaminergic dysfunction has been demonstrated during periods of substance use and abstinence. Specifically, during early abstinence (4 ± 2.59 days), greater difficulties with emotion regulation reported by MUD than CTL was found to positively correlate with D2-type dopamine receptor availability within amygdala (42). This finding is in line with previous evidence suggesting that D2type receptors in amygdala are thought to contribute to enhanced neural activity associated with a negative emotional state (96).…”

Section: Positron Emission Tomographysupporting

confidence: 87%

Dark Times: The Role of Negative Reinforcement in Methamphetamine Addiction

2020

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Methamphetamine use is associated with substantial adverse outcomes including poor mental and physical health, financial difficulties, and societal costs. Despite deleterious long-term consequences associated with methamphetamine, many people use drugs for short-term reduction of unpleasant physical or emotional sensations. By removing these aversive states, drug use behaviors are negatively reinforced. Abstinence from methamphetamine can then result in a return to previous aversive emotional states linked to withdrawal and craving, often contributing to an increased likelihood for relapse. This negative reinforcement cycle is hypothesized to be a motivating and maintaining factor for addiction. Thus, this review highlights the current evidence for negative reinforcement mechanisms in methamphetamine use disorder by integrating studies of subjective experience, behavior, functional magnetic resonance imaging, positron emission tomography, and event-related potentials and examining the efficacy of treatments targeting aspects of negative reinforcement. Overall, the literature demonstrates that individuals who use methamphetamine have diminished cognitive control and process emotions, loss of reward, and interoceptive information differently than non-using individuals. These differences are reflected in behavioral and subjective experiments as well as brain-based experiments which report significant differences in various frontal regions, insula, anterior cingulate cortex, and striatum. Together, the results suggest methamphetamine users have an altered experience of negative outcomes, difficulties employing effective emotion regulation, and difficulty engaging in adaptive or goal-directed decision-making. Suggestions for future research to improve our understanding of how negative reinforcement contributes to methamphetamine addiction and to develop effective interventions are provided.

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Section: Positron Emission Tomographysupporting

confidence: 87%

Dark Times: The Role of Negative Reinforcement in Methamphetamine Addiction

2020

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“…There were 19 studies assessing dopamine receptor availability in 342 stimulant users and 321 healthy controls (7 studies in amphetamine-like stimulant users 20,21,38–42 and 12 studies in cocaine users 16–19,22,37,43–48). …”

Section: Resultsmentioning

confidence: 99%

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine

et al. 2017

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Importance Stimulant use disorder is common, affecting between 0.3 to 1.1% of the population, and costs over $85 billion per year globally. There are currently no licensed treatments. Several lines of evidence implicate the dopamine system in the pathophysiology of substance use disorder. Thus understanding the nature of dopamine dysfunction seen in stimulant users has the potential to aid the development of new therapeutics. Objective To comprehensively review the in-vivo imaging evidence for dopaminergic alterations in stimulant (cocaine or amphetamine/methamphetamine) drug abuse or dependence. Data sources The entire PubMed, EMBASE and PsycINFO databases were searched for studies from inception date to May 14, 2016. Study selection A total of 31 studies were identified that compared dopaminergic measures between 519 stimulant users and 512 controls using positron emission tomography or single-photon emission computed tomography to measure striatal dopamine synthesis or release, or dopamine transporter or receptor availability. Data extraction and synthesis Demographic, clinical and imaging measures were extracted from each study and meta-analyses and sensitivity analyses were conducted for stimulants combined and cocaine and amphetamines separately where there were sufficient studies. Main Outcomes and Measures We determined the difference in dopamine release (assessed using change in the D2/3 receptor availability following administration of amphetamine or methylphenidate), transporter and receptor availability in cocaine, amphetamine and methamphetamine users and healthy controls. Results In majority of the studies the duration of abstinence varied from 5 days to 3 weeks. There was a significant decrease in striatal dopamine release (stimulants combined: Hedge’s g= −0.84; cocaine: −0.87, both p<0.001), dopamine transporter availability (stimulants combined: Hedge’s g= −0.91, p<0.01; amphetamine and methamphetamine: Hedge’s g: −1.47, p<0.001) and D2/3 availability (stimulants combined: Hedge’s g= −0.76; cocaine: −0.73; amphetamine and methamphetamine: −0.81, all p<0.001). We did not find consistent alterations in vesicular monoamine transporter, dopamine synthesis or D1 receptor studies. Conclusion and relevance Our data suggest that both pre and post-synaptic aspects of the dopamine system in the striatum are down-regulated in stimulant users. We discuss the commonality and difference between these findings and the discrepancies with the preclinical literature as well as their implications for future drug development.

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“…Group differences were also observed in limbic and paralimbic regions. The elevated amygdalar DA 2/3 R availability in high EXT participants may lead to difficulties in emotion regulation [15] and altered appetitive responses to cues associated with drugs and other rewards [51]. However, the contribution of these DA 2/3 Rs might be complex: in laboratory animals, their stimulation decreases impulsive behaviors and incentive motivational effects [52,53], while also increasing cocaine-seeking behaviors [54].…”

Section: Discussionmentioning

confidence: 99%

Extra-striatal D2/3 receptor availability in youth at risk for addiction

Jaworska

Cox

Tippler

et al. 2020

Neuropsychopharmacol.

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The neurobiological traits that confer risk for addictions remain poorly understood. However, dopaminergic function throughout the prefrontal cortex, limbic system, and upper brainstem has been implicated in behavioral features that influence addiction vulnerability, including poor impulse control, and altered sensitivity to rewards and punishments (i.e., externalizing features). To test these associations in humans, we measured type-2/3 dopamine receptor (DA 2/3 R) availability in youth at high vs. low risk for substance use disorders (SUDs). In this study, N = 58 youth (18.5 ± 0.6 years) were recruited from cohorts that have been followed since birth. Participants with either high (high EXT; N = 27; 16 F/11 M) or low pre-existing externalizing traits (low EXT; N = 31; 20 F/11 M) underwent a 90-min positron emission tomography [ 18 F]fallypride scan, and completed the Barratt Impulsiveness Scale (BIS-11), Substance Use Risk Profile scale (SURPS), and Sensitivity to Punishment (SP) and Sensitivity to Reward (SR) questionnaire. We found that high vs. low EXT trait participants reported elevated substance use, BIS-11, SR, and SURPS impulsivity scores, had a greater prevalence of psychiatric disorders, and exhibited higher [ 18 F]fallypride binding potential (BP ND) values in prefrontal, limbic and paralimbic regions, even when controlling for substance use. Group differences were not evident in midbrain dopamine cell body regions, but, across all participants, low midbrain BP ND values were associated with low SP scores. Together, the results suggest that altered DA 2/3 R availability in terminal extra-striatal and dopamine cell body regions might constitute biological vulnerability traits, generating an EXT trajectory for addictions with and without co-occurring alterations in punishment sensitivity (i.e., an internalizing feature).

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

Cited by 25 publications

References 70 publications

Dark Times: The Role of Negative Reinforcement in Methamphetamine Addiction

Dark Times: The Role of Negative Reinforcement in Methamphetamine Addiction

Association of Stimulant Use With Dopaminergic Alterations in Users of Cocaine, Amphetamine, or Methamphetamine

Extra-striatal D2/3 receptor availability in youth at risk for addiction

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