Evidence for Dopamine Abnormalities in the Substantia Nigra in Cocaine Addiction Revealed by Neuromelanin-Sensitive MRI

Cassidy, Clifford; Carpenter, Kenneth M.; Konova, Anna B.; Cheung, Victoria; Grassetti, Alexander; Zecca, Luigi; Abi‐Dargham, Anissa; Martínez, Diana; Horga, Guillermo

doi:10.1176/appi.ajp.2020.20010090

Cited by 35 publications

(22 citation statements)

References 41 publications

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“…This all fits previous findings with PET imaging that dopamine synthesis in the nigrostriatal pathway is increased in schizophrenia and related to positive symptoms [2]. A recent study also provides a first indication NM-MRI signal is increased in the SN in cocaine addiction [28]. Hence, NM-MRI appears to be a potential biomarker for dopamine dysfunction in psychiatric disorders.…”

Section: Neuromelanin Sensitive Mri (Nm-mri)supporting

confidence: 89%

“…NM-MRI is an upcoming MRI technique that enables in vivo visualization of the substantia nigra pars compacta (SN). It has gained increasing interest due to the role of the SN in a variety dopaminergic disorders, including schizophrenia, cocaine addiction, Huntington's and Parkinson's disease (PD) [26][27][28]. The SN in the mesencephalon is the location from where dopaminergic neurons project to the striatum forming the nigrostriatal pathway.…”

Section: Neuromelanin Sensitive Mri (Nm-mri)mentioning

confidence: 99%

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Imaging of the dopamine system with focus on pharmacological MRI and neuromelanin imaging

Reneman

Pluijm

Schrantee

et al. 2021

European Journal of Radiology

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The dopamine system in the brain is involved in a variety of neurologic and psychiatric disorders, such as Parkinson's disease, attention-deficit/hyperactivity disorder and psychosis. Different aspects of the dopamine system can be visualized and measured with positron emission tomography (PET) and single photon emission computed tomography (SPECT), including dopamine receptors, dopamine transporters, and dopamine release. New developments in MR imaging also provide proxy measures of the dopamine system in the brain, offering alternatives with the advantages MR imaging, i.e. no radiation, lower costs, usually less invasive and time consuming. This review will give an overview of these developments with a focus on the most developed techniques: pharmacological MRI (phMRI) and neuromelanin sensitive MRI (NM-MRI). PhMRI is a collective term for functional MRI techniques that administer a pharmacological challenge to assess its effects on brain hemodynamics. By doing so, it indirectly assesses brain neurotransmitter function such as dopamine function. NM-MRI is an upcoming MRI technique that enables in vivo visualization and semi-quantification of neuromelanin in the substantia nigra. Neuromelanin is located in the cell bodies of dopaminergic neurons of the nigrostriatal pathway and can be used as a proxy measure for long term dopamine function or degeneration of dopaminergic neurons. Both techniques are still primarily used in clinical research, but there is promise for clinical application, in particular for NM-MRI in dopaminergic neurodegenerative diseases like Parkinson's disease.

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Section: Neuromelanin Sensitive Mri (Nm-mri)supporting

confidence: 89%

Section: Neuromelanin Sensitive Mri (Nm-mri)mentioning

confidence: 99%

Imaging of the dopamine system with focus on pharmacological MRI and neuromelanin imaging

Reneman

Pluijm

Schrantee

et al. 2021

European Journal of Radiology

View full text Add to dashboard Cite

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“…However, obtaining these in vivo proxies of dopamine function is challenging in patient populations, since the needed radiopharmaceuticals render these measures highly expensive, invasive and time-consuming. Technological advances, such as improved signal intensity and increased signal-to-noise ratio recently enabled neuromelanin-sensitive magnetic resonance imaging (NM-MRI) as a possible readily available window into molecular alterations in psychiatric disorders in vivo (6,7).…”

Section: Introductionmentioning

confidence: 99%

Neuromelanin-Sensitive Magnetic Resonance Imaging in Schizophrenia: A Meta-Analysis of Case-Control Studies

et al. 2021

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Background: Psychiatry is in urgent need of reliable biomarkers. Novel neuromelanin-sensitive magnetic resonance imaging (NM-MRI) sequences provide a time-efficient and non-invasive way to investigate the human brain in-vivo. This gives insight into the metabolites of dopaminergic signaling and may provide further evidence for potential dopaminergic alterations in patients with schizophrenia (SCZ). The present systematic review provides a meta-analysis of case-control studies using neuromelanin-sensitive sequences in SCZ vs. healthy controls (HC).Methods: According to predefined search terms and inclusion criteria studies were extracted on PubMed. Meta-analyses with a fixed and random-effects model with inverse variance method, DerSimonian-Laird estimator for τ2, and Cohen's d were calculated. Bias was assessed using funnel plots. The primary study outcome was contrast-to-noise ratio (CNR) in the substantia nigra compared between HC and SCZ.Results: The total sample of k = 6 studies included n = 183 cases and n = 162 controls. Across all studies we found a significant elevation of CNR in the substantia nigra (d = 0.42 [0.187; 0.655], z = 3.521, p < 0.001) in cases compared to controls. We found no significant difference in the control region of locus coeruleus (d = −0.07 [−0.446; 0.302], z = −0.192, p = 0.847), with CNR for the latter only reported in k = 3 studies.Conclusion: CNR in the substantia nigra were significantly elevated in cases compared to controls. Our results support neuromelanin as a candidate biomarker for dopaminergic dysfunction in schizophrenia. Further studies need to assess this candidate marker in large, longitudinal cohorts and address potential effects of disease state, medication and correlations with symptoms.

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“…The SNr is the ventral part of the substantia nigra. Recent evidence has implied that abnormalities of the substantia nigra are involved in the pathophysiology of addiction ( Sharpe et al, 2014 ; Cassidy et al, 2020 ), and acute methamphetamine administration could induce neuronal death in the substantia nigra ( Sabrini et al, 2020 ). The substantia nigra also plays a crucial role in the relapse to drug seeking ( Hyman et al, 2006 ; Madsen et al, 2012 ; Pelloux et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

High-Frequency Deep Brain Stimulation of the Substantia Nigra Pars Reticulata Facilitates Extinction and Prevents Reinstatement of Methamphetamine-Induced Conditioned Place Preference

et al. 2021

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Persistent and stable drug memories lead to a high rate of relapse among addicts. A number of studies have found that intervention in addiction-related memories can effectively prevent relapse. Deep brain stimulation (DBS) exhibits distinct therapeutic effects and advantages in the treatment of neurological and psychiatric disorders. In addition, recent studies have also found that the substantia nigra pars reticulata (SNr) could serve as a promising target in the treatment of addiction. Therefore, the present study aimed to investigate the effect of DBS of the SNr on the reinstatement of drug-seeking behaviors. Electrodes were bilaterally implanted into the SNr of rats before training of methamphetamine-induced conditioned place preference (CPP). High-frequency (HF) or low-frequency (LF) DBS was then applied to the SNr during the drug-free extinction sessions. We found that HF DBS, during the extinction sessions, facilitated extinction of methamphetamine-induced CPP and prevented drug-primed reinstatement, while LF DBS impaired the extinction. Both HF and LF DBS did not affect locomotor activity or induce anxiety-like behaviors of rats. Finally, HF DBS had no effect on the formation of methamphetamine-induced CPP. In conclusion, our results suggest that HF DBS of the SNr could promote extinction and prevent reinstatement of methamphetamine-induced CPP, and the SNr may serve as a potential therapeutic target in the treatment of drug addiction.

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Evidence for Dopamine Abnormalities in the Substantia Nigra in Cocaine Addiction Revealed by Neuromelanin-Sensitive MRI

Cited by 35 publications

References 41 publications

Imaging of the dopamine system with focus on pharmacological MRI and neuromelanin imaging

Imaging of the dopamine system with focus on pharmacological MRI and neuromelanin imaging

Neuromelanin-Sensitive Magnetic Resonance Imaging in Schizophrenia: A Meta-Analysis of Case-Control Studies

High-Frequency Deep Brain Stimulation of the Substantia Nigra Pars Reticulata Facilitates Extinction and Prevents Reinstatement of Methamphetamine-Induced Conditioned Place Preference

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