Progress in Neuro-Psychopharmacology and Biological Psychiatry
Review articleConditioned and sensitized responses to stimulant drugs in humans
Section snippets
Background
Almost by definition the development of pathological drug taking is characterized by progressively more frequent and more easily initiated bouts of drug use. Based on studies conducted in laboratory animals, it has been proposed that this altered tendency reflects enhanced incentive salience of the drug-paired cues and increased motivational responses to the drug. In rodents, the best studied neurobiological correlates of these changes are conditioned and sensitized drug-induced activations of
Drug-induced dopamine release and behavioral significance
A large body of animal research indicates that most compulsively abused drugs activate the mesolimbic DA system (Di Chiara and Imperato, 1988). These drug-induced increases in extracellular DA levels are greater following self-administration behavior than after passive, non-contingent administration of the drug (Smith et al., 1980, Smith et al., 1982, Kiyatkin and Stein, 1995, Di Ciano et al., 1996, Hemby et al., 1997). The behavioral effects of increased limbic DA transmission include enhanced
Evidence for drug cue-induced dopamine release in individuals with substance dependence
The first attempt to measure changes in DA release in human striatum in response to drug cues was by Childress and colleagues (1992). The study used SPECT with [123I]IBZM, and measured responses in 10 recently abstinent (6 to 51 days), treatment seeking patients meeting criteria for cocaine dependence. Statistically significant effects were not found, possibly reflecting the limited anatomical resolution of the method.
More recently, two PET [11C]raclopride studies have tested whether exposure
Summary and conclusions
Our understanding of the contribution of DA neurotransmission to the acquisition of drug taking and the development and maintenance of substance abuse remains in its early stages. One model, based on studies conducted in laboratory animals, proposes that drug-induced activation of the mesolimbic DA system increases the incentive salience of drug-paired events. Repeated exposure to addictive drugs leads to a progressive increase in the ability of the drug and drug-paired cues to activate these
Acknowledgements
The author thanks Dr. Paul Vezina for many helpful discussions, Drs. Jane Stewart and Paul B. Clarke for feedback on an earlier version of the paper, Fonds de la recherche en santé du Québec (FRSQ) for a salary award, and the McGill University for the William Dawson Scholar addiction research chair.
References (195)
- et al.
Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naive healthy volunteers: results from a large cohort
Eur Neuropsychopharmacol
(2003) - et al.
Memory processes governing amphetamine-induced psychomotor sensitization
Neuropsychopharmacology
(2002) - et al.
Brain substrates for increased drug seeking during protracted withdrawal
Neuropharmacology
(2004) - et al.
Psychostimulant withdrawal as an inducing condition in animal models of depression
Neurosci Biobehav Rev
(2005) - et al.
A ‘crash’ course on psychostimulant withdrawal as a model of depression
Trends Pharmacol Sci
(2002) - et al.
Haloperidol antagonism of cue-elicited cocaine craving
The Lancet
(1996) - et al.
What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience?
Brain Res Rev
(1998) - et al.
Parsing reward
Trends Neurosci
(2003) Attention-deficit/hyperactivity disorder: a selective overview
Biol Psychiatry
(2005)- et al.
Dopamine functions in appetitive and defensive behaviours
Prog Neurobiology
(1992)
Subjective responses to d-amphetamine alone and after pimozide pretreatment in normal, healthy volunteers
Biol Psychiatry
High dose pimozide does not block amphetamine-induced euphoria in normal volunteers
Pharmacol Biochem Behav
Acute effects of cocaine on human brain activity and emotion
Neuron
Self detoxification by amphetamine dependent patients: a pilot study
Drug Alc Depend
Behavioral changes and [123I]IBZM equilibrium SPECT measurement of amphetamine-induced dopamine release in rhesus monkeys exposed to subchronic amphetamine
Neuropsychopharmacology
Changes in basal and cocaine-evoked extracellular dopamine uptake and release in the rat nucleus accumbens during early abstinence from cocaine: quantitative determination under transient conditions
Neuroscience
Can induced moods trigger drug-related responses in opiate abuse patients?
J Subst Abuse Treat
Subjective reports of withdrawal among cocaine users: recommendations for DSM-IV
Drug Alcohol Depend
New concepts in cocaine addiction: the dopamine depletion hypothesis
Neurosci Biobehav Rev
Dopamine release in human ventral striatum and expectation of reward
Behav Brain Res
Acute administration of d-amphetamine decreases impulsivity in healthy volunteers
Neuropsychopharmacology
Inhibition of dopamine efflux in the rat nucleus accumbens during abstinence after free access to d-amphetamine
Behavioral Brain Research
Amphetamine-induced dopamine release in human ventral striatum correlates with euphoria
Biol Psychiatry
Effects of cocaine context on NAcc dopamine and behavioral activity after repeated intravenous cocaine administration
Brain Res
Acute effects of oral cocaine on inhibitory control of behavior in humans
Drug Alcohol Depend
Effects of d-amphetamine on behavioral control in stimulant abusers: the role of prepotent response tendencies
Drug Alcohol Depend
Residual effects of repeated cocaine smoking in humans
Drug Alcohol Depend
Conditioned increases in mesolimbic dopamine overflow associated with cocaine
Brain Res
Frequency of recent cocaine and alcohol use affects drug craving and associated responses to stress and drug-related cues
Psychoneuroendocrinology
The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking
Brain Res Rev
Drug preference and mood in humans: repeated assessment of d-amphetamine
Pharmacol Biochem Behav
Dopamine transmission in the initiation and expression of drug-induced sensitization of motor activity
Brain Res Rev
Memory and addiction: shared neural circuitry and molecular mechanisms
Neuron
The effects of repeated amphetamine exposure on multiple measures of human behavior
Pharmacol Biochem Behav
Fluctuations in nucleus accumbens dopamine during cocaine self-administration behavior: an in vivo electrochemical study
Neuroscience
The stimulation of central kappa opioid receptors decreases male sexual behavior and locomotor activity
Brain Res
Amphetamine-induced increases in extracellular dopamine, drug wanting, and novelty seeking: a PET/[11C]raclopride study in healthy men
Neuropsychopharmacology
Diagnostic and statistical manual of mental disorders: DSM-IV
Sensitization to the psychomotor stimulant effects of amphetamine: modulation by associative learning
Behav Neurosci
Drug-induced neurobehavioral plasticity: the role of environmental context
Behavioural Pharmacology
Enduring enhancement of amphetamine sensitization by drug-associated environmental stimuli
J Pharmacol Exp Ther
Activity of striatal neurons reflects dynamic encoding and recoding of procedural memories
Nature
The hedonic response to cigarette smoking is proportional to dopamine release in the human striatum as measured by positron emission tomography and [11C]raclopride
Synapse
Morphine and cocaine exert common chronic actions on tyrosine hydroxylase in dopaminergic brain reward regions
J Neurochem
The debate over dopamine's role in reward: the case for incentive salience
Psychopharmacology
Alcohol promotes dopamine release in human nucleus accumbens
Synapse
Modeling sensitization to stimulants in humans: a [11C]raclopride/PET study in healthy volunteers
Arch Gen Psychiatry
Conditioned dopamine release in humans: a PET [11C]raclopride study with amphetamine
J Neuroscience
Personality changes in women recovering from substance-related dependence
J Addict Dis
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