1. ¹Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA
2. ²Department of Psychology, University of Minnesota, Minneapolis, MN, USA
3. ³Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
4. ⁴Behavioral Neuroscience Branch, IRP/NIDA/NIH/DHHS, Baltimore, MD, USA

Correspondence: Dr MJ Thomas, Departments of Neuroscience and Psychology, University of Minnesota, 6-145 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455, USA. E-mail: tmhomas@umn.edu

Received 20 November 2007; Revised 11 December 2007; Accepted 13 February 2008; Published online 17 March 2008.

Abstract

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.