From inhibition to excitation: functional effects of interaction between opioid receptors

Life Sci. 2004 Dec 17;76(5):479-85. doi: 10.1016/j.lfs.2004.09.012.


Opioids have excitatory effects in multiple regions of the nervous system. Excitation by opioids is generally attributed to inhibition of inhibitory pathways (disinhibition). However, recent studies indicate that opioids can directly excite individual cells. These effects may occur when opioid receptors interact with other G protein coupled receptors, when different subtypes of opioid receptors interact, or when opioids transactivate other receptors such as receptor tyrosine kinases. Changes in the relative level of expression of different receptors in an individual cell may therefore determine its functional response to a given ligand. This phenomenon could represent an adaptive mechanism involved in tolerance, dependence and subsequent withdrawal.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Drug Tolerance / physiology
  • Humans
  • Narcotic Antagonists
  • Narcotics / pharmacology*
  • Opioid-Related Disorders / metabolism
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Opioid* / agonists
  • Receptors, Opioid* / physiology
  • Substance Withdrawal Syndrome / metabolism


  • Narcotic Antagonists
  • Narcotics
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid