Dopamine D1 Receptors in Cocaine Dependence Measured with PET and the Choice to Self-Administer Cocaine

Martínez, Diana; Slifstein, Mark; Narendran, Rajesh; Foltin, Richard W.; Broft, Allegra; Hwang, Dah‐Ren; Perez, Audrey; Abi‐Dargham, Anissa; Fischman, Marian W.; Kleber, Herbert D.; Laruelle, Marc

doi:10.1038/npp.2008.235

Cited by 127 publications

(59 citation statements)

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“…With PET and the radiotracer [ 11 C] NNC 112, Martinez et al [86] found no difference between cocaine abusers and normal controls. However, within the cocaine abusers, low D1 receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D1 receptor availability may be associated with an increased risk of -8-hydroxy-3-methyl-1-phenyl -2,3,4,5-tetrahydro-1H-3-benzazepine], the first selective D1-like receptor antagonist, is recognized as the standard ligand for PET studies of striatal D1 receptors [87] .…”

Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

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Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

et al. 2014

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Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction remains unclear. Positron emission tomography (PET) is the fi rst technology used for in vivo measurement of components of the dopaminergic system in the human brain. In this article, we review the major fi ndings from PET imaging studies on the involvement of DA in drug addiction, including presynaptic DA synthesis, vesicular monoamine transporter 2, the DA transporter, and postsynaptic DA receptors. These results have corroborated the role of DA in addiction and increased the understanding of its underlying mechanisms.Keywords: dopamine; dopaminergic system; drug addiction; positron emission tomography ·Review· Brain Dopaminergic System Dopamine (DA) is a catecholamine neurotransmitter in the nervous system. It has many functions in the brain, including punishment, reward, voluntary movement, mood, attention, motivation, sleep, working memory, and learning [1] .DA is synthesized by the hydroxylation and decarboxylation of L-tyrosine in DA neurons and, before being released into the synapse in response to an action potential, it is stored within presynaptic vesicles (Fig. 1). The action of DA occurs by binding to postsynaptic DA receptors, resulting in the formation of second messengers. There are fi ve subtypes of DA receptors, which can be grouped into two classes or families: D1-like and D-2 like [1,2] . The D1-like receptor family comprises the D1 and D5 receptors, encoded by genes with no introns, acting by way of Gs-proteins and activating adenylyl cyclase, thus increasing cAMP production [3,4] .The D2-like receptor family comprises the D2, D3, and D4 receptors, encoded by genes containing introns. D2-like receptors act via Gi-proteins, inhibit adenylyl cyclase activity, and thus decrease cAMP activity [3,5] .The action of DA in the synapse is terminated primarily by reuptake to the presynaptic membrane through the dopamine transporter (DAT) [6] . Otherwise, DA is partially removed by oxidation by monoamine oxidase orcatechol-O-methyltransferase in the synaptic cleft (Fig. 1).T h e d o p a m i n e r g i c n e u r o n s , w h o s e p r i m a r y neurotransmitter is DA, interconnect many areas of the brain to form a system which originates in the substantia nigra (SN) pars compacta, ventral tegmental area (VTA), and hypothalamus. The dopaminergic system is typically divided into four major pathways: mesocortical (from the VTA to the frontal cortex), mesolimbic (from the VTA to the nucleus accumbens), nigrostriatal (from the SN to the striatum), and tuberoinfundibular (from the hypothalamus to the pituitary gland). The mesostriatal and mesocortical pathways are currently recognized to contribute most to drug addiction [7] . Neurosci Bull October 1, 2014, 30(5): 765-776 766 Drug AddictionThe term addiction is derived from the Latin verb addicere, which referred to the Roman court action of binding a person to another. From the 17th century, addiction has been used to refer to psychoactive substances (...

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Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

“…With PET and the radiotracer [ 11 C] NNC 112, Martinez et al [86] found no difference between cocaine abusers and normal controls. However, studies of striatal D1 receptors [87] .…”

Section: Pet Studies Of Postsynaptic Da Receptorsmentioning

confidence: 99%

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

et al. 2014

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“…Blunted pre-synaptic dopamine release, specifically in the ventral striatum, has been associated with increased cocaine-seeking behavior (Martinez et al, 2007b). In this study, cocaine abusers underwent PET imaging scans to measure pre-synaptic dopamine release, followed by laboratory sessions in which the choice was presented between cocaine and an alternative reinforcer.…”

Section: Utilizing Pet To Elucidate Mechanistic Biomarkersmentioning

confidence: 99%

Biomarkers for the Development of New Medications for Cocaine Dependence

Bough

Amur

Lao

et al. 2013

Neuropsychopharmacol

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There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)-another type of defined DDT-is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.

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“…With PET and the radiotracer [ 11 C] NNC 112, Martinez et al (2009) did not find difference between cocaine abusers and the normals. However, within the cocaine abusers, low D1 receptor availability in the ventral striatum was associated with the choice to self-administer cocaine, suggesting that low D1 receptor availability may be associated with an increased risk of relapse in cocaine dependence.…”

Section: Assessment Of Da Receptors Of the Dopaminergic Systemmentioning

confidence: 89%

Positron Emission Tomography Molecular Imaging of Dopaminergic System in Drug Addiction

Hou¹,

Tian²,

Zhang³

2012

The Anatomical Record

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Dopamine (DA) is involved in drug reinforcement, but its role in drug addiction remains unclear. Positron emission tomography (PET) is the first technology used for the direct measurement of components of the dopaminergic system in the living human brain. In this article, we reviewed the major findings of PET imaging studies on the involvement of DA in drug addiction, especially in heroin addiction. Furthermore, we summarized PET radiotracers that have been used to study the role of DA in drug addiction. To investigate presynaptic function in drug addiction, PET tracers have been developed to measure DA synthesis and transport. For the investigation of postsynaptic function, several radioligands targeting dopamine one (D1) receptor and dopamine two (D2) receptor are extensively used in PET imaging studies. Moreover, we also summarized the PET imaging findings of heroin addiction studies, including heroin-induced DA increases and the reinforcement, role of DA in the long-term effects of heroin abuse, DA and vulnerability to heroin abuse and the treatment implications. PET imaging studies have corroborated the role of DA in drug addiction and increase our understanding the mechanism of drug addiction. Anat Rec, 295:722-733, 2012. V C 2012 Wiley Periodicals, Inc.Key words: positron emission tomography; dopamine; dopamine receptor; drug addiction; heroin BRAIN DOPAMINERGIC SYSTEM Dopamine (DA) is a catecholamine neurotransmitter in the nervous system that permits individual nerve fibers (neurons) to communicate with each other. DA has many functions in the brain, including important roles in behavior and cognition, voluntary movement, motivation, punishment and reward, sleep, mood, attention, working memory, and learning (Smythies, 2005).

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Dopamine D1 Receptors in Cocaine Dependence Measured with PET and the Choice to Self-Administer Cocaine

Cited by 127 publications

References 51 publications

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

Brain dopaminergic system changes in drug addiction: a review of positron emission tomography findings

Biomarkers for the Development of New Medications for Cocaine Dependence

Positron Emission Tomography Molecular Imaging of Dopaminergic System in Drug Addiction

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