G protein-coupled receptor kinase/beta-arrestin systems and drugs of abuse: psychostimulant and opiate studies in knockout mice

Neuromolecular Med. 2004;5(1):41-50. doi: 10.1385/NMM:5:1:041.


G protein-coupled receptors (GPCRs) currently represent pharmaceutical targets for numerous medicinal compounds that are used to treat conditions ranging from blood pressure dysregulation to depression to pain, demonstrating the wide range of functions mediated by this receptor family. GPCR activation is determined not only by the initiation of signaling cascades but also by regulatory mechanisms that control the extent and duration of their signals. The balance of activation and desensitization dictate the ultimate physiological response to both endogenous and exogenous receptor stimuli. Therefore, these mechanisms may play a particularly relevant role during chronic exposure to agonists such as in conditions when drugs are abused. Two major classes of drugs of abuse, opiates and psychostimulants, both use either direct or indirect GPCR signaling mechanisms to mediate their effects. Therefore, the regulation of GPCRs may have bearing on the neuronal adaptations that underlie the reinforcing properties of drugs of abuse.

Publication types

  • Review

MeSH terms

  • Animals
  • Arrestins / drug effects
  • Arrestins / metabolism*
  • Brain Chemistry / drug effects*
  • Brain Chemistry / genetics
  • Central Nervous System Stimulants / pharmacology
  • Cyclic GMP-Dependent Protein Kinases / drug effects
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Humans
  • Illicit Drugs / pharmacology*
  • Mice
  • Mice, Knockout
  • Narcotics / pharmacology
  • Receptors, G-Protein-Coupled / drug effects
  • Receptors, G-Protein-Coupled / metabolism*
  • Substance-Related Disorders / genetics
  • Substance-Related Disorders / metabolism*
  • Substance-Related Disorders / physiopathology
  • beta-Arrestins


  • Arrestins
  • Central Nervous System Stimulants
  • Illicit Drugs
  • Narcotics
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • Cyclic GMP-Dependent Protein Kinases