title: Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse.
abstract: Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.) esa.korpi@helsinki.fi gavin_dawe@nuhs.edu.sg.
authors.forename: Esa R
authors.initials: ER
authors.lastname: Korpi
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
authors.forename: Bjørnar
authors.initials: B
authors.lastname: den Hollander
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
authors.forename: Usman
authors.initials: U
authors.lastname: Farooq
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
authors.forename: Elena
authors.initials: E
authors.lastname: Vashchinkina
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
authors.forename: Ramamoorthy
authors.initials: R
authors.lastname: Rajkumar
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.).
authors.forename: Petri
authors.initials: P
authors.lastname: Hyytiä
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland (E.R.K., B.d.H., E.V., P.H.); Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, and SINAPSE, Singapore Institute for Neurotechnology, Singapore (E.R.K., R.R., G.S.D.); Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut (U.F.); and Centre for Neuropsychopharmacology, Division of Brain Sciences, Burlington Danes Building, Imperial College London, London. United Kingdom (D.J.N.) esa.korpi@helsinki.fi gavin_dawe@nuhs.edu.sg.
authors.forename: Gavin S
authors.initials: GS
authors.lastname: Dawe
mesh_terms: D000437:Alcoholism / Q000503:physiopathology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology; D001569:Benzodiazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology*; D002186:Cannabinoids / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003863:Depression / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006213:Hallucinogens / Q000494:pharmacology; D006801:Humans; D013287:Illicit Drugs; D009294:Narcotics / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism; D059906:Neuroimaging; D009473:Neuronal Plasticity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D019966:Substance-Related Disorders / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000662:Amphetamines; D002186:Cannabinoids; D006213:Hallucinogens; D013287:Illicit Drugs; D009294:Narcotics; D009414:Nerve Growth Factors; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D001569:Benzodiazepines; C069452:alpha-amino-3-carboxymethoxy-5-methyl-4-isoxazolepropionic acid; D009538:Nicotine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D003042:Cocaine