The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans

Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs.

[1]  Brent G. Nelson,et al.  Frontal Hyperconnectivity Related to Discounting and Reversal Learning in Cocaine Subjects , 2011, Biological Psychiatry.

[2]  S. Hyman,et al.  Addiction, Dopamine, and the Molecular Mechanisms of Memory , 2000, Neuron.

[3]  Patrick E. Rothwell,et al.  Integrating synaptic plasticity and striatal circuit function in addiction , 2012, Current Opinion in Neurobiology.

[4]  R K Siegel,et al.  Cocaine hallucinations. , 1978, The American journal of psychiatry.

[5]  B. Balleine,et al.  Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning , 2004, The European journal of neuroscience.

[6]  K. Lynch,et al.  Results of an initial clinical trial of varenicline for the treatment of cocaine dependence. , 2012, Drug and alcohol dependence.

[7]  E. Baca-García,et al.  Executive dysfunction in chronic cocaine users: an exploratory study. , 2011, Drug and alcohol dependence.

[8]  R. Sinha,et al.  Immune system inflammation in cocaine dependent individuals: implications for medications development , 2012, Human psychopharmacology.

[9]  Yihong Yang,et al.  Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity , 2010, NeuroImage.

[10]  S. Hyman,et al.  Acute Effects of Cocaine on Human Brain Activity and Emotion , 1997, Neuron.

[11]  J. Javitch,et al.  Amphetamine and Methamphetamine Differentially Affect Dopamine Transporters in Vitro and in Vivo* , 2009, Journal of Biological Chemistry.

[12]  Hugh Garavan,et al.  Executive Dysfunction in Cocaine Addiction: Evidence for Discordant Frontal, Cingulate, and Cerebellar Activity , 2004, The Journal of Neuroscience.

[13]  G. Koob,et al.  Extended access cocaine self‐administration differentially activates dorsal raphe and amygdala corticotropin‐releasing factor systems in rats , 2012, Addiction biology.

[14]  A. Levey,et al.  Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users , 1996, Annals of neurology.

[15]  Alan A. Wilson,et al.  Increased Vesicular Monoamine Transporter Binding during Early Abstinence In Human Methamphetamine Users: Is VMAT2 a Stable Dopamine Neuron Biomarker? , 2008, The Journal of Neuroscience.

[16]  Streichenwein Sm,et al.  Am J Psychiatry , 1996 .

[17]  K. Brady,et al.  Impaired Cognitive Performance in Subjects with Methamphetamine Dependence during Exposure to Neutral versus Methamphetamine-Related Cues , 2012, The American journal of drug and alcohol abuse.

[18]  M. Iyo,et al.  Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. , 2001, The American journal of psychiatry.

[19]  I. Stolerman,et al.  Drugs of abuse: behavioural principles, methods and terms. , 1992, Trends in pharmacological sciences.

[20]  Andrea D Fass,et al.  Synthetic Cathinones (Bath Salts): Legal Status and Patterns of Abuse , 2012, The Annals of pharmacotherapy.

[21]  Peter W. Kalivas,et al.  An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: A pilot study , 2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[22]  J. Cadet,et al.  Methamphetamine Causes Microglial Activation in the Brains of Human Abusers , 2008, The Journal of Neuroscience.

[23]  N. Volkow,et al.  Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers , 1993, Synapse.

[24]  A. Sanjuán,et al.  Right parietal hypoactivation in a cocaine-dependent group during a verbal working memory task , 2011, Brain Research.

[25]  B. Rocha Stimulant and reinforcing effects of cocaine in monoamine transporter knockout mice. , 2003, European journal of pharmacology.

[26]  D. Sulzer,et al.  How Addictive Drugs Disrupt Presynaptic Dopamine Neurotransmission , 2011, Neuron.

[27]  A. Kelley Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning , 2004, Neuroscience & Biobehavioral Reviews.

[28]  T. Robbins,et al.  Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers , 2006, Psychopharmacology.

[29]  S. Hyman,et al.  Addiction and the brain: The neurobiology of compulsion and its persistence , 2001, Nature Reviews Neuroscience.

[30]  J. D. McGaugh Memory consolidation and the amygdala: a systems perspective , 2002, Trends in Neurosciences.

[31]  R. Mattick,et al.  A double-blind, placebo-controlled trial of modafinil (200 mg/day) for methamphetamine dependence. , 2009, Addiction.

[32]  Larry A. Kramer,et al.  Diffusion Tensor Imaging and Decision Making in Cocaine Dependence , 2010, PloS one.

[33]  Cheuk Y. Tang,et al.  Decreasing Striatal 6-FDOPA Uptake with Increasing Duration of Cocaine Withdrawal , 1997, Neuropsychopharmacology.

[34]  B. Everitt,et al.  Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex , 2002, Neuroscience & Biobehavioral Reviews.

[35]  K. Berridge,et al.  What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? , 1998, Brain Research Reviews.

[36]  E. Vittinghoff,et al.  Mirtazapine to reduce methamphetamine use: a randomized controlled trial. , 2011, Archives of general psychiatry.

[37]  Lian Zhang,et al.  Loss of striatal vesicular monoamine transporter protein (VMAT2) in human cocaine users. , 2003, The American journal of psychiatry.

[38]  Robinson Jb Stereoselectivity and isoenzyme selectivity of monoamine oxidase inhibitors: Enantiomers of amphetamine, n-methylamphetamine and deprenyl , 1985 .

[39]  T. Robbins,et al.  Neural systems of reinforcement for drug addiction: from actions to habits to compulsion , 2005, Nature Neuroscience.

[40]  L. Amato,et al.  Antidepressants for cocaine dependence and problematic cocaine use. , 2011, The Cochrane database of systematic reviews.

[41]  S. Sesack,et al.  Anatomical substrates for glutamate-dopamine interactions: evidence for specificity of connections and extrasynaptic actions. , 2003, Annals of the New York Academy of Sciences.

[42]  M. LaVoie,et al.  Dopamine Quinone Formation and Protein Modification Associated with the Striatal Neurotoxicity of Methamphetamine: Evidence against a Role for Extracellular Dopamine , 1999, The Journal of Neuroscience.

[43]  Lianne Schmaal,et al.  N-Acetylcysteine Normalizes Glutamate Levels in Cocaine-Dependent Patients: A Randomized Crossover Magnetic Resonance Spectroscopy Study , 2012, Neuropsychopharmacology.

[44]  S. Ross,et al.  The Neurobiology of Addictive Disorders , 2009, Clinical neuropharmacology.

[45]  R. A. Fuchs,et al.  Subregion‐specific role of glutamate receptors in the nucleus accumbens on drug context‐induced reinstatement of cocaine‐seeking behavior in rats , 2012, Addiction biology.

[46]  E. Cone,et al.  Elimination of cocaine and metabolites in plasma, saliva, and urine following repeated oral administration to human volunteers. , 2000, Journal of analytical toxicology.

[47]  J. Lépine,et al.  New treatments for cocaine dependence: a focused review. , 2008, The international journal of neuropsychopharmacology.

[48]  Sara R. Jones,et al.  Presynaptic dopamine modulation by stimulant self-administration. , 2013, Frontiers in bioscience.

[49]  P. Kalivas,et al.  N‐Acetyl Cysteine‐Induced Blockade of Cocaine‐Induced Reinstatement , 2003, Annals of the New York Academy of Sciences.

[50]  W. Ling,et al.  Medications development: successes and challenges. , 2005, Pharmacology & therapeutics.

[51]  G. Koob The role of CRF and CRF-related peptides in the dark side of addiction , 2010, Brain Research.

[52]  S. Evans,et al.  Treatment of cocaine dependent treatment seekers with adult ADHD: double-blind comparison of methylphenidate and placebo. , 2007, Drug and alcohol dependence.

[53]  Charles T. Taylor,et al.  Combining computerized home-based treatments for generalized anxiety disorder: an attention modification program and cognitive behavioral therapy. , 2012, Behavior therapy.

[54]  N. Fox,et al.  Attention bias modification treatment for pediatric anxiety disorders: a randomized controlled trial. , 2012, The American journal of psychiatry.

[55]  G. Di Chiara,et al.  Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[56]  N. Volkow,et al.  Effects of route of administration on cocaine induced dopamine transporter blockade in the human brain. , 2000, Life sciences.

[57]  David E. Moorman,et al.  Lateral Hypothalamic Orexin/hypocretin Neurons: a Role in Reward-seeking and Addiction , 2009 .

[58]  Ming D. Li,et al.  Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial. , 2012, Addiction.

[59]  G. Chiara,et al.  Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments , 1999, Neuroscience.

[60]  Colleen A. Hanlon,et al.  Elevated gray and white matter densities in cocaine abstainers compared to current users , 2011, Psychopharmacology.

[61]  K. Berridge,et al.  The neural basis of drug craving: An incentive-sensitization theory of addiction , 1993, Brain Research Reviews.

[62]  B. Greenberg,et al.  Anatomy and physiology of the basal ganglia: Implications for DBS in psychiatry , 2008, Neuroscience & Biobehavioral Reviews.

[63]  M. Gold,et al.  Neurobiology of tobacco smoking and other addictive disorders. , 1999, The Psychiatric clinics of North America.

[64]  G. Bartzokis,et al.  Choreoathetoid movements in cocaine dependence , 1999, Biological Psychiatry.

[65]  K. Rice,et al.  Amphetamine‐type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin , 2001, Synapse.

[66]  Stephen J. Kish,et al.  Pharmacologic mechanisms of crystal meth , 2008, Canadian Medical Association Journal.

[67]  J. Bradshaw,et al.  Addiction, compulsive drug seeking, and the role of frontostriatal mechanisms in regulating inhibitory control , 2010, Neuroscience & Biobehavioral Reviews.

[68]  I. Grant,et al.  Longer term improvement in neurocognitive functioning and affective distress among methamphetamine users who achieve stable abstinence , 2010, Journal of clinical and experimental neuropsychology.

[69]  T. Robinson,et al.  Enduring changes in brain and behavior produced by chronic amphetamine administration: A review and evaluation of animal models of amphetamine psychosis , 1986, Brain Research Reviews.

[70]  M. Kuhar,et al.  Cocaine inhibition of ligand binding at dopamine, norepinephrine and serotonin transporters: a structure-activity study. , 1990, Life sciences.

[71]  Samuel M. McClure,et al.  A computational substrate for incentive salience , 2003, Trends in Neurosciences.

[72]  G. Koob Neural Mechanisms of Drug Reinforcement a , 1992, Annals of the New York Academy of Sciences.

[73]  E. D. De Souza,et al.  Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport. , 1991, The Journal of pharmacology and experimental therapeutics.

[74]  E. Nestler,et al.  Transcriptional and epigenetic mechanisms of addiction , 2011, Nature Reviews Neuroscience.

[75]  C. Mathis,et al.  In vivo evidence for low striatal vesicular monoamine transporter 2 (VMAT2) availability in cocaine abusers. , 2012, The American journal of psychiatry.

[76]  Steven E. Hyman,et al.  Revolution Stalled , 2012, Science Translational Medicine.

[77]  Yiyun Huang,et al.  Cocaine Dependence and D2 Receptor Availability in the Functional Subdivisions of the Striatum: Relationship with Cocaine-Seeking Behavior , 2004, Neuropsychopharmacology.

[78]  Paul M. Thompson,et al.  Structural Abnormalities in the Brains of Human Subjects Who Use Methamphetamine , 2004, The Journal of Neuroscience.

[79]  G F Koob,et al.  Drug abuse: hedonic homeostatic dysregulation. , 1997, Science.

[80]  S. Hyman Addiction: a disease of learning and memory. , 2005, The American journal of psychiatry.

[81]  J. Cadet,et al.  Methamphetamine toxicity and messengers of death , 2009, Brain Research Reviews.

[82]  Rita Z. Goldstein,et al.  Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers , 2010, PloS one.

[83]  J. Mariani,et al.  Psychostimulant treatment of cocaine dependence. , 2012, The Psychiatric clinics of North America.

[84]  T L Faber,et al.  Neural activity related to drug craving in cocaine addiction. , 2001, Archives of general psychiatry.

[85]  Colleen A. Hanlon,et al.  Loss of laterality in chronic cocaine users: An fMRI investigation of sensorimotor control , 2010, Psychiatry Research: Neuroimaging.

[86]  D. Ciccarone Stimulant abuse: pharmacology, cocaine, methamphetamine, treatment, attempts at pharmacotherapy. , 2011, Primary care.

[87]  P. Kalivas,et al.  Drug Addiction as a Pathology of Staged Neuroplasticity , 2008, Neuropsychopharmacology.

[88]  M. Höfler,et al.  Associations between use of cocaine, amphetamines, or psychedelics and psychotic symptoms in a community sample , 2011, Acta psychiatrica Scandinavica.

[89]  A. Waters,et al.  Galantamine improves sustained attention in chronic cocaine users. , 2011, Experimental and clinical psychopharmacology.

[90]  R. Wise Action of drugs of abuse on brain reward systems , 1980, Pharmacology Biochemistry and Behavior.

[91]  G. Rebec,et al.  Lidocaine Inactivation of Ventral Subiculum Attenuates Cocaine-Seeking Behavior in Rats , 2003, The Journal of Neuroscience.

[92]  R. Roth,et al.  Topographical organization of the efferent projections of the medial prefrontal cortex in the rat: An anterograde tract‐tracing study with Phaseolus vulgaris leucoagglutinin , 1989, The Journal of comparative neurology.

[93]  K. Carroll,et al.  Effects of galantamine on cocaine use in chronic cocaine users. , 2011, The American journal on addictions.

[94]  E. Rolls The representation of information about faces in the temporal and frontal lobes , 2007, Neuropsychologia.

[95]  G. Rylander Psychoses and the punding and choreiform syndromes in addiction to central stimulant drugs. , 1972, Psychiatria, neurologia, neurochirurgia.

[96]  S. Purdon,et al.  Predictors of psychosis severity in individuals with primary stimulant addictions. , 2011, Addictive behaviors.

[97]  J. M. Ree,et al.  Pharmacological treatments for heroin and cocaine addiction , 2003, European Neuropsychopharmacology.

[98]  A. Dale,et al.  Dorsal anterior cingulate cortex: A role in reward-based decision making , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[99]  O. Kitamura Detection of methamphetamine neurotoxicity in forensic autopsy cases. , 2009, Legal medicine.

[100]  L. Amato,et al.  Dopamine agonists for the treatment of cocaine dependence. , 2015, The Cochrane database of systematic reviews.

[101]  R. See,et al.  The neurocircuitry of addiction: an overview , 2008, British journal of pharmacology.

[102]  F. Gawin Cocaine abuse and addiction. , 1989, The Journal of family practice.

[103]  S. Totterdell,et al.  Basolateral amygdala efferents to the ventral subiculum preferentially innervate pyramidal cell dendritic spines , 2003, Brain Research.

[104]  A. Smit,et al.  The synaptic pathology of drug addiction. , 2012, Advances in experimental medicine and biology.

[105]  R. North,et al.  Two types of neurone in the rat ventral tegmental area and their synaptic inputs. , 1992, The Journal of physiology.

[106]  N. Uretsky,et al.  The importance of calcium in the amphetamine-induced stimulation of dopamine synthesis in mouse striata in vivo. , 1982, The Journal of pharmacology and experimental therapeutics.

[107]  S. Sesack,et al.  Anatomical Substrates for Glutamate‐Dopamine Interactions , 2003 .

[108]  Udi E. Ghitza,et al.  Clonidine blocks stress-induced craving in cocaine users , 2011, Psychopharmacology.

[109]  Reese T. Jones,et al.  The bioavailability of intranasal and smoked methamphetamine , 2003, Clinical pharmacology and therapeutics.

[110]  Walter Ling,et al.  Bupropion for the Treatment of Methamphetamine Dependence , 2008, Neuropsychopharmacology.

[111]  K. Berridge Faculty Opinions recommendation of Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction. , 2008 .

[112]  T. Robbins,et al.  Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans , 2008, Psychopharmacology.

[113]  M W Fischman,et al.  Crack cocaine and cocaine hydrochloride. Are the differences myth or reality? , 1996, JAMA.

[114]  A. Levey,et al.  Striatal dopamine nerve terminal markers in human, chronic methamphetamine users , 1996, Nature Medicine.

[115]  G. Uhl,et al.  Meta-analysis and genome-wide interpretation of genetic susceptibility to drug addiction , 2011, BMC Genomics.

[116]  A. Mayer,et al.  Enhanced cue reactivity and fronto-striatal functional connectivity in cocaine use disorders. , 2011, Drug and alcohol dependence.

[117]  M. Witter,et al.  Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin , 1987, Neuroscience.

[118]  K. Kantak,et al.  Cognitive enhancers for facilitating drug cue extinction: Insights from animal models , 2011, Pharmacology Biochemistry and Behavior.

[119]  Barry J. Everitt,et al.  Psychomotor Stimulant Addiction: A Neural Systems Perspective , 2002, The Journal of Neuroscience.

[120]  A. Copeland,et al.  Differences between methamphetamine users and cocaine users in treatment. , 2001, Drug and alcohol dependence.

[121]  Chris Cruickshank,et al.  A review of the clinical pharmacology of methamphetamine. , 2009, Addiction.

[122]  M. Banich,et al.  Medial Orbitofrontal Cortex Gray Matter Is Reduced in Abstinent Substance-Dependent Individuals , 2009, Biological Psychiatry.

[123]  P. Rucci,et al.  Aripiprazole and ropinirole treatment for cocaine dependence: evidence from a pilot study. , 2011, Current pharmaceutical design.

[124]  A. Grace,et al.  Amphetamine Activation of Hippocampal Drive of Mesolimbic Dopamine Neurons: A Mechanism of Behavioral Sensitization , 2008, The Journal of Neuroscience.

[125]  S. Sesack,et al.  Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area , 1992, The Journal of comparative neurology.

[126]  R. A. Fuchs,et al.  Prefrontal cortical regulation of drug seeking in animal models of drug relapse. , 2010, Current topics in behavioral neurosciences.

[127]  M. Le Moal,et al.  Addiction and the brain antireward system. , 2008, Annual review of psychology.

[128]  R. De La Garza,et al.  Relationship between gender and psychotic symptoms in cocaine-dependent and methamphetamine-dependent participants. , 2010, Gender medicine.

[129]  S. Kubo,et al.  Microglial and astrocytic changes in the striatum of methamphetamine abusers. , 2010, Legal medicine.

[130]  A. Bentivoglio,et al.  Cocaine addiction: from habits to stereotypical-repetitive behaviors and punding. , 2008, Drug and alcohol dependence.

[131]  S. Totterdell,et al.  Individual nucleus accumbens-projection neurons receive both basolateral amygdala and ventral subicular afferents in rats , 2003, Neuroscience.

[132]  W. van den Brink,et al.  Pharmacological treatments for heroin and cocaine addiction. , 2003, European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology.

[133]  M. Reivich,et al.  Limbic activation during cue-induced cocaine craving. , 1999, The American journal of psychiatry.

[134]  P. Kalivas The glutamate homeostasis hypothesis of addiction , 2009, Nature Reviews Neuroscience.

[135]  W. Ling,et al.  Randomized, double-blind, placebo-controlled trial of modafinil for the treatment of methamphetamine dependence. , 2010, Drug and alcohol dependence.

[136]  P. Kalivas,et al.  Is cocaine desire reduced by N-acetylcysteine? , 2007, The American journal of psychiatry.

[137]  R. Wise,et al.  Cocaine Experience Establishes Control of Midbrain Glutamate and Dopamine by Corticotropin-Releasing Factor: A Role in Stress-Induced Relapse to Drug Seeking , 2005, The Journal of Neuroscience.

[138]  T. Rubino,et al.  The role of the endogenous cannabinoid system in drug addiction. , 2008, Drug news & perspectives.

[139]  P. Clarke,et al.  Segregation of Amphetamine Reward and Locomotor Stimulation between Nucleus Accumbens Medial Shell and Core , 2003, The Journal of Neuroscience.

[140]  Diana Martinez,et al.  Cocaine abuse and sensitization of striatal dopamine transmission: A critical review of the preclinical and clinical imaging literature , 2008, Synapse.

[141]  I. Grant,et al.  Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence. , 2005, Neuropsychology.

[142]  Gregory V. Simpson,et al.  Computerized Cognitive Training Restores Neural Activity within the Reality Monitoring Network in Schizophrenia , 2012, Neuron.

[143]  C. Drenzek,et al.  Methamphetamine Use and Methicillin-Resistant Staphylococcus aureus Skin Infections , 2007, Emerging infectious diseases.

[144]  T. Robbins,et al.  Dopamine Release in the Dorsal Striatum during Cocaine-Seeking Behavior under the Control of a Drug-Associated Cue , 2002, The Journal of Neuroscience.

[145]  N. Volkow,et al.  The neural basis of addiction: a pathology of motivation and choice. , 2005, The American journal of psychiatry.

[146]  G. Rudnick,et al.  From synapse to vesicle: the reuptake and storage of biogenic amine neurotransmitters. , 1993, Biochimica et biophysica acta.

[147]  G. C. Wagner,et al.  Methamphetamine-induced neuronal damage: A possible role for free radicals , 1989, Neuropharmacology.

[148]  J. Samet,et al.  Food and Drug Administration , 2007, BMJ : British Medical Journal.

[149]  R. Mark Wightman,et al.  Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter , 1996, Nature.

[150]  R. A. Fuchs,et al.  Effects of mGluR1 antagonism in the dorsal hippocampus on drug context-induced reinstatement of cocaine-seeking behavior in rats , 2009, Psychopharmacology.

[151]  C. Roncero,et al.  Efficacy of psychostimulant drugs for cocaine dependence. , 2010, The Cochrane database of systematic reviews.

[152]  D. Nichols,et al.  Differences between the mechanism of action of MDMA, MBDB, and the classic hallucinogens. Identification of a new therapeutic class: entactogens. , 1986, Journal of psychoactive drugs.

[153]  N. Volkow,et al.  Addiction: Beyond dopamine reward circuitry , 2011, Proceedings of the National Academy of Sciences.

[154]  Mark Slifstein,et al.  Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. , 2007, The American journal of psychiatry.

[155]  D. Sibley,et al.  Medication discovery for addiction: translating the dopamine D3 receptor hypothesis. , 2012, Biochemical pharmacology.

[156]  R. Gainetdinov,et al.  Cocaine self-administration in dopamine-transporter knockout mice , 1998, Nature Neuroscience.

[157]  A. Waters,et al.  Cognitive enhancement as a treatment for drug addictions , 2013, Neuropharmacology.

[158]  R. Wightman,et al.  Mechanisms of Amphetamine Action Revealed in Mice Lacking the Dopamine Transporter , 1998, The Journal of Neuroscience.

[159]  H. Fibiger,et al.  Feeding-evoked dopamine release in the nucleus accumbens: regulation by glutamatergic mechanisms , 1997, Neuroscience.

[160]  P. Kalivas,et al.  Cystine/glutamate exchange serves as the source for extracellular glutamate: Modifications by repeated cocaine administration , 2002, Amino Acids.

[161]  D. Rusyniak Neurologic manifestations of chronic methamphetamine abuse. , 2011, Neurologic clinics.

[162]  R. Vertes,et al.  Nucleus reuniens of the midline thalamus: Link between the medial prefrontal cortex and the hippocampus , 2007, Brain Research Bulletin.

[163]  R. Wise Dopamine and reward: The anhedonia hypothesis 30 years on , 2008, Neurotoxicity Research.

[164]  T. Robbins,et al.  Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[165]  M. Sofuoglu,et al.  Cognitive enhancement as a pharmacotherapy target for stimulant addiction. , 2010, Addiction.

[166]  K. Berridge,et al.  The Mind of an Addicted Brain: Neural Sensitization of Wanting Versus Liking , 1995 .

[167]  G. Bartzokis,et al.  White-matter abnormalities in brain during early abstinence from methamphetamine abuse , 2010, Psychopharmacology.

[168]  N. Volkow,et al.  Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence , 2001, The Journal of Neuroscience.

[169]  L. Jarrard What does the hippocampus really do? , 1995, Behavioural Brain Research.

[170]  D. Mash,et al.  Radioligand binding and immunoautoradiographic evidence for a lack of toxicity to dopaminergic nerve terminals in human cocaine overdose victims , 1997, Brain Research.

[171]  W. Hall,et al.  Amphetamine-related harms and treatment preferences of regular amphetamine users in Sydney, Australia. , 1997, Drug and alcohol dependence.

[172]  G. Aston-Jones,et al.  Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats , 2012, Psychopharmacology.

[173]  L. Parsons,et al.  Endocannabinoid influence in drug reinforcement, dependence and addiction-related behaviors. , 2011, Pharmacology & therapeutics.

[174]  K. Gysling Relevance of both type-1 and type-2 corticotropin releasing factor receptors in stress-induced relapse to cocaine seeking behaviour. , 2012, Biochemical pharmacology.

[175]  J S Fowler,et al.  Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex. , 2001, The American journal of psychiatry.

[176]  George Bartzokis,et al.  Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research , 2000, Psychiatry Research: Neuroimaging.

[177]  D. Sulzer,et al.  Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[178]  T. Robbins,et al.  The basolateral amygdala-ventral striatal system and conditioned place preference: Further evidence of limbic-striatal interactions underlying reward-related processes , 1991, Neuroscience.

[179]  E. Butelman,et al.  Pharmacotherapy of addictions , 2002, Nature Reviews Drug Discovery.

[180]  D. Kuhn,et al.  Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines , 2004, Neuroscience Letters.

[181]  B. Rounsaville,et al.  The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study. , 2010, The American journal on addictions.

[182]  K. J. Rhee,et al.  Choreoathetoid disorder associated with amphetamine-like drugs. , 1988, The American journal of emergency medicine.

[183]  M. Iyo,et al.  Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. , 2003, The American journal of psychiatry.

[184]  J. Kleinman,et al.  Fewer dopamine transporter receptors in the prefrontal cortex of cocaine users. , 1994, The American journal of psychiatry.

[185]  R. Wise,et al.  Brain dopamine and reward. , 1989, Annual review of psychology.

[186]  T. Kosten,et al.  Pharmacogenetic Treatments for Drug Addiction: Cocaine, Amphetamine and Methamphetamine , 2009, The American journal of drug and alcohol abuse.

[187]  I. Grant,et al.  Visual memory in methamphetamine-dependent individuals: deficient strategic control of encoding and retrieval , 2012, The Australian and New Zealand journal of psychiatry.

[188]  M. Haney,et al.  Aripiprazole maintenance increases smoked cocaine self-administration in humans , 2011, Psychopharmacology.

[189]  Y. Shaham,et al.  Neurobiology of Relapse to Heroin and Cocaine Seeking: A Review , 2002, Pharmacological Reviews.

[190]  B. Everitt,et al.  Dissociable Effects of Antagonism of NMDA and AMPA/KA Receptors in the Nucleus Accumbens Core and Shell on Cocaine-seeking Behavior , 2001, Neuropsychopharmacology.

[191]  J. Loftis,et al.  Methamphetamine Causes Persistent Immune Dysregulation: A Cross-Species, Translational Report , 2011, Neurotoxicity Research.

[192]  J S Fowler,et al.  Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers. , 2001, The American journal of psychiatry.

[193]  M. Preiss,et al.  Comparison of Wisconsin Card Sorting Test results between Czech subjects dependent on methamphetamine versus healthy volunteers. , 2012, Psychiatria Danubina.

[194]  R. Sunahara,et al.  Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction. , 2012, Future medicinal chemistry.

[195]  D. Sulzer,et al.  Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation of Dopamine Synthesis , 2002, The Journal of Neuroscience.

[196]  A. Cho,et al.  Pharmacokinetic and pharmacodynamic analysis of the actions of D-amphetamine and D-methamphetamine on the dopamine terminal. , 1995, The Journal of pharmacology and experimental therapeutics.

[197]  L. Swanson,et al.  Combinatorial amygdalar inputs to hippocampal domains and hypothalamic behavior systems , 2001, Brain Research Reviews.

[198]  T. Jay Dopamine: a potential substrate for synaptic plasticity and memory mechanisms , 2003, Progress in Neurobiology.

[199]  A. Grace,et al.  Dopamine-Dependent Interactions between Limbic and Prefrontal Cortical Plasticity in the Nucleus Accumbens: Disruption by Cocaine Sensitization , 2005, Neuron.

[200]  A Kübler,et al.  Cocaine dependence and attention switching within and between verbal and visuospatial working memory , 2005, The European journal of neuroscience.

[201]  Daniele Lecca,et al.  Dopamine and drug addiction: the nucleus accumbens shell connection , 2004, Neuropharmacology.

[202]  M. Álvaro-Bartolomé,et al.  Molecular adaptations of apoptotic pathways and signaling partners in the cerebral cortex of human cocaine addicts and cocaine-treated rats , 2011, Neuroscience.

[203]  Yongmin Chang,et al.  Impairments of facial emotion recognition and theory of mind in methamphetamine abusers , 2011, Psychiatry Research.

[204]  T. Kosten,et al.  Immunotherapy for drug abuse. , 2011, CNS & neurological disorders drug targets.

[205]  T. Insel Next-Generation Treatments for Mental Disorders , 2012, Science Translational Medicine.

[206]  S. J. Gatley,et al.  Decreased striatal dopaminergic responsiveness in detoxified cocaine-dependent subjects , 1997, Nature.

[207]  Y. Shaham,et al.  The reinstatement model of drug relapse: history, methodology and major findings , 2003, Psychopharmacology.

[208]  T. Robbins,et al.  Differential control over cocaine-seeking behavior by nucleus accumbens core and shell , 2004, Nature Neuroscience.

[209]  Michael H. Buonocore,et al.  Cognitive Control and White Matter Callosal Microstructure in Methamphetamine-Dependent Subjects: A Diffusion Tensor Imaging Study , 2009, Biological Psychiatry.

[210]  Rajita Sinha,et al.  Chronic Stress, Drug Use, and Vulnerability to Addiction , 2008, Annals of the New York Academy of Sciences.

[211]  D. Sulzer,et al.  Mechanisms of neurotransmitter release by amphetamines: A review , 2005, Progress in Neurobiology.

[212]  J. B. Robinson Stereoselectivity and isoenzyme selectivity of monoamine oxidase inhibitors. Enantiomers of amphetamine, N-methylamphetamine and deprenyl. , 1985, Biochemical pharmacology.

[213]  D. Ciraulo,et al.  Cocaine Rapid Efficacy Screening Trials (CREST): lessons learned. , 2005, Addiction.

[214]  A. Minassian,et al.  Effect of methamphetamine dependence on everyday functional ability. , 2010, Addictive behaviors.