Cracking the molecular code of cocaine addiction

ILAR J. 2011;52(3):309-20. doi: 10.1093/ilar.52.3.309.


Cocaine addiction is a behavioral disorder defined by behavioral symptoms that set it apart from nondisordered forms of drug use. Here we review evidence in rats (the most frequently used animal model in the field) that it is possible, after extended (but not after limited) access to cocaine for self-administration, to selectively induce some of these behaviors: gradual escalation of cocaine intake, enhanced motivation for the drug despite increased costs (or negative consequences), and increased sensitivity to drug- and stress-primed craving-like behavior. Animals with extended drug use also present selective neurocognitive deficits (e.g., compromised working memory) that may impair their ability to regulate cocaine intake. In some rats, extended access to cocaine for self-administration is associated with loss of control over cocaine intake, as assessed by continued drug use despite the opportunity to make a different choice and to the exclusion of more natural and rewarding activities. These rats may represent the most advanced and severe stage on the path to cocaine addiction. Finally, comparisons of rats with extended versus limited access to cocaine for self-administration have recently revealed the existence of a new molecular pathway in the dorsal striatum (a brain region altered in cocaine-addicted humans) that causally and selectively controls cocaine intake. This pathway involves unforeseen homeostatic interactions between microRNAs (a class of nonprotein-coding RNAs) and some key molecular regulators of neuronal plasticity (e.g., MeCP2 and BDNF). This discovery provides an entirely new direction for the development of effective antiaddiction treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Behavior, Addictive
  • Brain / metabolism
  • Cocaine*
  • Cocaine-Related Disorders* / metabolism
  • Humans
  • Neuronal Plasticity
  • Self Administration


  • Cocaine