Protein kinases and addiction.
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.
Lee
Anna M
AM
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, CA 94608, USA.
Messing
Robert O
RO
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*
D000697:Central Nervous System Stimulants; D013287:Illicit Drugs; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D047428:Protein Kinase Inhibitors; D000431:Ethanol; D011494:Protein Kinases