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  • Neuroplasticity in the mesolimbic dopamine system and cocaine addiction
  • Thomas MJ; Kalivas PW; Shaham Y
  • Br J Pharmacol 2008[May]; 154 (2): 327-42
  • The main characteristics of cocaine addiction are compulsive drug use despite adverse consequences and high rates of relapse during periods of abstinence. A current popular hypothesis is that compulsive cocaine use and cocaine relapse is due to drug-induced neuroadaptations in reward-related learning and memory processes, which cause hypersensitivity to cocaine-associated cues, impulsive decision making and abnormal habit-like learned behaviours that are insensitive to adverse consequences. Here, we review results from studies on the effect of cocaine exposure on selected signalling cascades, growth factors and physiological processes previously implicated in neuroplasticity underlying normal learning and memory. These include the extracellular signal-regulated kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF), glutamate transmission, and synaptic plasticity (primarily in the form of long-term potentiation and depression, LTP and LTD). We also discuss the degree to which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours, as assessed in animal models of drug addiction. Finally, we speculate on how these factors may interact to initiate and sustain cocaine psychomotor sensitization and cocaine seeking.
  • |*Neuronal Plasticity[MESH]
  • |*Synaptic Transmission[MESH]
  • |Animals[MESH]
  • |Behavior, Addictive/drug therapy/*metabolism/physiopathology[MESH]
  • |Behavior, Animal[MESH]
  • |Brain-Derived Neurotrophic Factor/metabolism[MESH]
  • |Cocaine-Related Disorders/drug therapy/*metabolism/physiopathology/psychology[MESH]
  • |Dopamine/*metabolism[MESH]
  • |Extracellular Signal-Regulated MAP Kinases/metabolism[MESH]
  • |Glutamic Acid/metabolism[MESH]
  • |Humans[MESH]
  • |Limbic System/enzymology/*metabolism[MESH]
  • |Models, Animal[MESH]
  • |Neural Pathways/metabolism/physiopathology[MESH]
  • |Psychomotor Performance[MESH]
  • |Recurrence[MESH]

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    *<b>[ Neuroplasticity in the mesolimbic dopamine system and cocaine addiction ]</b> Br J Pharmacol 2008; 154(2) ; 327-42 Thomas MJ; Kalivas PW; Shaham Y


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    Br J Pharmacol

    327 2.154 2008