Cellular and synaptic adaptations mediating opioid dependence

John Williams, M. J. Christie, O. Manzoni

Research output: Contribution to journalArticle

645 Citations (Scopus)

Abstract

Although opioids are highly effective for the treatment of pain, they are also known to be intensely addictive. There has been a massive research investment in the development of opioid analgesics, resulting in a plethora of compounds with varying affinity and efficacy at all the known opioid receptor subtypes. Although compounds of extremely high potency have been produced, the problem of tolerance to and dependence on these agonists persists. This review centers on the adaptive changes in cellular and synaptic function induced by chronic morphine treatment. The initial steps of opioid action are mediated through the activation of G protein-linked receptors. As is true for all G protein-linked receptors, opioid receptors activate and regulate multiple second messenger pathways associated with effector coupling, receptor trafficking, and nuclear signaling. These events are critical for understanding the early events leading to nonassociative tolerance and dependence. Equally important are associative and network changes that affect neurons that do not have opioid receptors but that are indirectly altered by opioid-sensitive cells. Finally, opioids and other drugs of abuse have some common cellular and anatomical pathways. The characterization of common pathways affected by different drugs, particularly after repeated treatment, is important in the understanding of drug abuse.

Original languageEnglish (US)
Pages (from-to)299-343
Number of pages45
JournalPhysiological Reviews
Volume81
Issue number1
StatePublished - 2001

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Opioid Analgesics
Opioid Receptors
GTP-Binding Proteins
Street Drugs
Second Messenger Systems
Cytoplasmic and Nuclear Receptors
Morphine
Substance-Related Disorders
Therapeutics
Neurons
Pain
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Physiology

Cite this

Cellular and synaptic adaptations mediating opioid dependence. / Williams, John; Christie, M. J.; Manzoni, O.

In: Physiological Reviews, Vol. 81, No. 1, 2001, p. 299-343.

Research output: Contribution to journalArticle

Williams, J, Christie, MJ & Manzoni, O 2001, 'Cellular and synaptic adaptations mediating opioid dependence', Physiological Reviews, vol. 81, no. 1, pp. 299-343.
Williams, John ; Christie, M. J. ; Manzoni, O. / Cellular and synaptic adaptations mediating opioid dependence. In: Physiological Reviews. 2001 ; Vol. 81, No. 1. pp. 299-343.
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