Reduced Dopamine Response to Amphetamine in Subjects at Ultra-High Risk for Addiction

Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses. We measured amphetamine-induced changes in [11C]raclopride binding in...

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Published inBiological psychiatry (1969) Vol. 76; no. 1; pp. 23 - 30
Main Authors Casey, Kevin F., Benkelfat, Chawki, Cherkasova, Mariya V., Baker, Glen B., Dagher, Alain, Leyton, Marco
Format Journal Article
LanguageEnglish
Published New York, NY Elsevier Inc 01.07.2014
Elsevier
Subjects
[11C]raclopride
Addictive behaviors
Adult and adolescent clinical studies
Amphetamine - pharmacology
Biological and medical sciences
Case-Control Studies
Central Nervous System Stimulants - pharmacology
Corpus Striatum - diagnostic imaging
Corpus Striatum - metabolism
Dopamine
Dopamine - metabolism
Dopamine Antagonists
Drug addiction
Family Health
Female
Functional Neuroimaging
Humans
Male
Medical sciences
PET
Positron-Emission Tomography
Prodromal Symptoms
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Raclopride
stimulants
substance dependence
Substance-Related Disorders - diagnosis
Substance-Related Disorders - diagnostic imaging
vulnerability
Young Adult
stimulants
Dopamine
vulnerability
[11C]raclopride
PET
substance dependence
[ 11C]raclopride
Amphetamine derivatives
Radionuclide study
High risk
Psychotropic
Central nervous system
Encephalon
Amfetamine
Drug of abuse
[
C]raclopride
Human
Drug addiction
Raclopride
CNS stimulant
Dopamine antagonist
Substance abuse
Vulnerability
Catecholamine
Biological fixation
D2 Dopamine receptor
Addiction
Young adult
Neurotransmitter
Positron emission tomography
Emission tomography
[C]raclopride
Online AccessGet full text

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Abstract Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses. We measured amphetamine-induced changes in [11C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15). Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [11C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences. Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
AbstractList Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses. We measured amphetamine-induced changes in [11C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15). Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [11C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences. Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
Background Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses. Methods We measured amphetamine-induced changes in [11 C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders ( n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction ( n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems ( n = 15). Results Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [11 C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences. Conclusions Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses. We measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15). Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences. Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses.BACKGROUNDNot everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use problems. In part, this might reflect perturbed mesolimbic dopamine responses.We measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15).METHODSWe measured amphetamine-induced changes in [(11)C]raclopride binding in 1) high-risk young adults with a multigenerational FH of substance use disorders (n = 16); 2) stimulant drug-naïve healthy control subjects with no known risk factors for addiction (n = 17); and 3) subjects matched to the high-risk group on personal drug use but without a FH of substance use problems (n = 15).Compared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences.RESULTSCompared with either control group, the high-risk young adults with a multigenerational FH of substance use disorders exhibited smaller [(11)C]raclopride responses, particularly within the right ventral striatum. Past drug use predicted the dopamine response also, but including it as a covariate increased the group differences.Together, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.CONCLUSIONSTogether, the results suggest that young people at familial high risk for substance use disorders have decreased dopamine responses to an amphetamine challenge, an effect that predates the onset of addiction.
Author Leyton, Marco
Cherkasova, Mariya V.
Baker, Glen B.
Dagher, Alain
Casey, Kevin F.
Benkelfat, Chawki
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  email: marco.leyton@mcgill.ca
  organization: Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec
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Issue 1
Keywords stimulants
Dopamine
vulnerability
[11C]raclopride
PET
substance dependence
[ 11C]raclopride
Amphetamine derivatives
Radionuclide study
High risk
Psychotropic
Central nervous system
Encephalon
Amfetamine
Drug of abuse
[
C]raclopride
Human
Drug addiction
Raclopride
CNS stimulant
Dopamine antagonist
Substance abuse
Vulnerability
Catecholamine
Biological fixation
D2 Dopamine receptor
Addiction
Young adult
Neurotransmitter
Positron emission tomography
Emission tomography
[C]raclopride
Language English
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2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.
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Snippet Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance use...
Background Not everyone who tries addictive drugs develops a substance use disorder. One of the best predictors of risk is a family history (FH) of substance...
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SubjectTerms [11C]raclopride
Addictive behaviors
Adult and adolescent clinical studies
Amphetamine - pharmacology
Biological and medical sciences
Case-Control Studies
Central Nervous System Stimulants - pharmacology
Corpus Striatum - diagnostic imaging
Corpus Striatum - metabolism
Dopamine
Dopamine - metabolism
Dopamine Antagonists
Drug addiction
Family Health
Female
Functional Neuroimaging
Humans
Male
Medical sciences
PET
Positron-Emission Tomography
Prodromal Symptoms
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Raclopride
stimulants
substance dependence
Substance-Related Disorders - diagnosis
Substance-Related Disorders - diagnostic imaging
vulnerability
Young Adult
Title Reduced Dopamine Response to Amphetamine in Subjects at Ultra-High Risk for Addiction
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https://www.clinicalkey.es/playcontent/1-s2.0-S0006322313008238
https://dx.doi.org/10.1016/j.biopsych.2013.08.033
https://www.ncbi.nlm.nih.gov/pubmed/24138922
https://www.proquest.com/docview/1535623227
Volume 76
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