title: Protein kinases and addiction.
abstract: Although drugs of abuse have different chemical structures and interact with different protein targets, all appear to usurp common neuronal systems that regulate reward and motivation. Addiction is a complex disease that is thought to involve drug-induced changes in synaptic plasticity due to alterations in cell signaling, gene transcription, and protein synthesis. Recent evidence suggests that drugs of abuse interact with and change a common network of signaling pathways that include a subset of specific protein kinases. The best studied of these kinases are reviewed here and include extracellular signal-regulated kinase, cAMP-dependent protein kinase, cyclin-dependent protein kinase 5, protein kinase C, calcium/calmodulin-dependent protein kinase II, and Fyn tyrosine kinase. These kinases have been implicated in various aspects of drug addiction including acute drug effects, drug self-administration, withdrawal, reinforcement, sensitization, and tolerance. Identifying protein kinase substrates and signaling pathways that contribute to the addicted state may provide novel approaches for new pharmacotherapies to treat drug addiction.
authors.affiliation: Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, CA 94608, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lee
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D013287:Illicit Drugs / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011494:Protein Kinases / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000502:physiology; D012201:Reward; D015398:Signal Transduction / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000201:enzymology / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000201:enzymology*
chemical_list: D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D047428:Protein Kinase Inhibitors; D000431:Ethanol; D011494:Protein Kinases