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 [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).
Results
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.
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.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Familial transmission of substance use disorders.Arch Gen Psychiatry. 1998; 55: 973-979
- Family history as a predictor of alcohol dependence.Alcohol Clin Exp Res. 1992; 16: 572-575
- Evaluating measures of family history of alcoholism: Density versus dichotomy.Addiction. 1998; 93: 1511-1520
- Functions of mesolimbic dopamine: Changing concepts and shifting paradigms.Psychopharmacology (Berl). 2007; 191: 389
- Parsing reward.Trends Neurosci. 2003; 26: 507-513
- Conditioned cues and the expression of stimulant sensitization in animals and humans.Neuropharmacology. 2009; 56: 160-168
- A selective role for dopamine in stimulus-reward learning.Nature. 2011; 469: 53-57
- Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.Proc Natl Acad Sci U S A. 1988; 85: 5274-5278
- Individual differences in behavioral measures: Correlations with nucleus accumbens dopamine measured by microdialysis.Pharmacol Biochem Behav. 1991; 39: 877-882
- Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: Genetic and motivational determinants.J Pharmacol Exp Ther. 1993; 267: 250-258
- Parallel strain-dependent effect of amphetamine on locomotor activity and dopamine release in the nucleus accumbens: An in vivo study in mice.Neuroscience. 1998; 82: 521-528
- Effects of morphine on metabolism of dopamine and serotonin in brains of alcohol-preferring AA and alcohol-avoiding ANA rats.Alcohol. 1999; 18: 3-10
- Neurochemical characteristics associated with ethanol preference in selected alcohol-preferring and -nonpreferring rats: A quantitative microdialysis study.Alcohol Clin Exp Res. 2001; 25: 198-205
- Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects.Nature. 1997; 386: 830-833
- Profound decreases in dopamine release in striatum in detoxified alcoholics: Possible orbitofrontal involvement.J Neurosci. 2007; 27: 12700-12706
- Alcohol dependence is associated with blunted dopamine transmission in the ventral striatum.Biol Psychiatry. 2005; 58: 779-786
- Amphetamine-induced dopamine release: Markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine.Am J Psychiatry. 2007; 164: 622-629
- Imaging dopamine transmission in cocaine dependence: Link between neurochemistry and response to treatment.Am J Psychiatry. 2011; 168: 634-641
- From first drug use to drug dependence: Developmental periods of risk for dependence upon marijuana, cocaine, and alcohol.Neuropsychopharmacology. 2002; 26: 479-488
- Probability and predictors of transition from first use to dependence on nicotine, alcohol, cannabis, and cocaine: Results of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).Drug Alcohol Depend. 2011; 115: 120-130
First MB, Spitzer RL, Gibbon M, Williams JBW (2002): Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition. (SCID-I/NP). New York: Biometrics Research, New York State Psychiatric Institute.
NIH (1992): Family Interview for Genetics Study (FIGS): A Manual for FIGS. Bethesda: National Institute of Mental Health, Clinical Neurogenetics Branch, Intramural Research Program.
- Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: A PET/ [11C]raclopride study in healthy men.Neuropsychopharmacology. 2002; 27: 1027-1035
- Modeling sensitization to stimulants in humans: An [11C]raclopride/positron emission tomography study in healthy men.Arch Gen Psychiatry. 2006; 63: 1386-1395
- Decreasing amphetamine-induced dopamine release by acute phenylalanine/tyrosine depletion: A PET/ [11C]raclopride study in healthy men.Neuropsychopharmacology. 2004; 29: 427-432
- A rapid method of determining amphetamine in plasma samples using pentafluorobenzenesulfonyl chloride and electron-capture gas chromatography.J Pharmacol Toxicol Methods. 2001; 46: 111-115
- Co-planar Stereotaxic Atlas of the Human Brain.Georg Thieme Verlag, Stuttgart, Germany1988
- Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space.J Comput Assist Tomogr. 1994; 18: 192-205
- Anatomical mapping of functional activation in stereotactic coordinate space.Neuroimage. 1992; 1: 43-53
- Motion correction of multi-frame PET data in neuroreceptor mapping: Simulation based validation.Neuroimage. 2009; 47: 1496-1505
- Parametric imaging of ligand-receptor binding in PET using a simplified reference region model.Neuroimage. 1997; 6: 279-287
- Consensus nomenclature for in vivo imaging of reversibly binding radioligands.J Cereb Blood Flow Metab. 2007; 27: 1533-1539
- Imaging synaptic neurotransmission with in vivo binding competition techniques: A critical review.J Cereb Blood Flow Metab. 2000; 20: 423-451
- Imaging D2 receptor occupancy by endogenous dopamine in humans.Neuropsychopharmacology. 1997; 17: 162-174
- Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates.Synapse. 1997; 25: 1-14
- A statistical method for the analysis of positron emission tomography neuroreceptor ligand data.Neuroimage. 2000; 12: 245-256
- A unified statistical approach for determining significant signals in images of cerebral activation.Hum Brain Mapp. 1996; 4: 58-73
- Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D(2) receptor parameter measurements in ventral striatum.J Cereb Blood Flow Metab. 2001; 21: 1034-1057
- Ecstasy and drug consumption patterns: A Canadian rave population study.Can J Psychiatry. 2002; 47: 546-551
- A review of the clinical pharmacology of methamphetamine.Addiction. 2009; 104: 1085-1099
- Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers.Synapse. 1993; 14: 169-177
- Decreases in dopamine receptors but not in dopamine transporters in alcoholics.Alcohol Clin Exp Res. 1996; 20: 1594-1598
- Low level of brain dopamine D2 receptors in methamphetamine abusers: Association with metabolism in the orbitofrontal cortex.Am J Psychiatry. 2001; 158: 2015-2021
- High levels of dopamine D2 receptors in unaffected members of alcoholic families: Possible protective factors.Arch Gen Psychiatry. 2006; 63: 999-1008
- Striatal dopamine release and family history of alcoholism.Alcohol Clin Exp Res. 2006; 30: 1143-1151
- Effect of cocaine self-administration on dopamine D2 receptors in rhesus monkeys.Synapse. 1998; 30: 88-96
- Variability in subjective responses to cocaine: Initial experiences of college students.Addict Behav. 1993; 18: 445-453
- Subjective responses to initial experience with cocaine: An exploration of the incentive-sensitization theory of drug abuse.Addiction. 2006; 101: 713-725
- Assessment of abuse liability of stimulant drugs in humans: A methodological survey.Drug Alcohol Depend. 1991; 28: 3-48
- Do initial responses to drugs predict future use or abuse?.Neurosci Biobehav Rev. 2012; 36: 1565-1576
- The neurobiology of desire: Dopamine and the regulation of mood and motivational states in humans.in: Kringelbach M.L. Berridge K.C. Pleasures of the Brain. Oxford University Press, New York2009: 222-243
- Dopamine, learning and motivation.Nat Rev Neurosci. 2004; 5: 483-494
- Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria.Biol Psychiatry. 2001; 49: 81-96
- Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naïve healthy volunteers: Results from a large cohort.Eur Neuropsychopharmacol. 2003; 13: 459-468
- SPECT imaging of striatal dopamine release after amphetamine challenge.J Nucl Med. 1995; 36: 1182-1190
- Reinforcing effects of psychostimulants in humans are associated with increases in brain dopamine and occupancy of D(2) receptors.J Pharmacol Exp Ther. 1999; 291: 409-415
- Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: Amphetamine-induced dopamine release in the functional subdivisions of the striatum.J Cereb Blood Flow Metab. 2003; 23: 285-300
- Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine.Neuropsychopharmacology. 2005; 30: 821-832
- Dopaminergic activity in depressed smokers: A positron emission tomography study.Synapse. 2009; 63: 681-689
- Impulsivity and chronic stress are associated with amphetamine-induced striatal dopamine release.Neuroimage. 2007; 36: 153-166
- Brain dopamine response in human opioid addiction.Br J Psychiatry. 2008; 193: 65-72
- Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin.Synapse. 2001; 39: 32-41
- The neurobiology of anhedonia and other reward-related deficits.Trends Neurosci. 2012; 35: 68-77
- Endogenous opioid release in the human brain reward system induced by acute amphetamine administration.Biol Psychiatry. 2012; 72: 371-377
- Conditioned and sensitized responses to stimulant drugs in humans.Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31: 1601-1613
- Psychiatric disorders in relatives of probands with opiate addiction.Arch Gen Psychiatry. 1991; 48: 33-42
- The familial aggregation of common psychiatric and substance use disorders in the National Comorbidity Survey: A family history study.Br J Psychiatry. 1997; 170: 541-548
- Specificity of genetic and environmental risk factors for use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates in male twins.Am J Psychiatry. 2003; 160: 687-695
- Familial transmission of substance dependence: Alcohol, marijuana, cocaine, and habitual smoking: A report from the Collaborative Study on the Genetics of Alcoholism.Arch Gen Psychiatry. 1998; 55: 982-988
- Co-occurrence of abuse of different drugs in men: The role of drug-specific and shared vulnerabilities.Arch Gen Psychiatry. 1998; 55: 967-972
- Enhanced morphine- and cocaine-induced behavioral sensitization in alcohol-preferring AA rats.Psychopharmacology (Berl). 1999; 142: 244-252
Article info
Publication history
Published online: October 21, 2013
Accepted:
August 29,
2013
Received in revised form:
August 6,
2013
Received:
October 16,
2012
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Blunted Dopamine Release as a Biomarker for Vulnerability for Substance Use DisordersBiological PsychiatryVol. 76Issue 1
- PreviewImaging of the striatal dopamine system continues to dominate studies using positron emission tomography (PET) in substance use disorders (SUD). A key reason for this is the stability of the findings: most studies imaging the dopamine D2 family of receptors (D2R) and stimulant-induced dopamine release show blunting of striatal dopamine transmission in subjects with addiction. This phenotype is seen across SUDs, including cocaine, nicotine, alcohol, opiate, and methamphetamine. Reduced binding at the D2R persists independently of many clinical factors, and this effect is maintained following days to months of abstinence.
- Full-Text
- Preview
