Opioid and Psychostimulant Plasticity: Targeting Overlap in Nucleus Accumbens Glutamate Signaling

Trends Pharmacol Sci. 2018 Mar;39(3):276-294. doi: 10.1016/j.tips.2017.12.004. Epub 2018 Jan 12.

Abstract

Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified theory of addiction that encompasses most abused substances. This unitary theory has recently been challenged - citing distinctions in structural neural plasticity, biochemical signaling, and neural circuitry to argue that addiction to opioids and psychostimulants is behaviorally and neurobiologically distinct. Recent more selective examination of drug-induced plasticity has highlighted that these two drug classes promote an overall reward circuitry signaling overlap through modifying excitatory synapses in the nucleus accumbens - a key constituent of the reward system. We discuss adaptations in presynaptic/postsynaptic and extrasynaptic glutamate signaling produced by opioids and psychostimulants, and their relevance to circuit remodeling and addiction-related behavior - arguing that these core neural adaptations are important targets for developing pharmacotherapies to treat addiction to multiple drugs.

Keywords: addiction; glutamate; nucleus accumbens; opioids; plasticity; psychostimulants.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / pharmacology*
  • Animals
  • Central Nervous System Stimulants / pharmacology*
  • Excitatory Amino Acid Agents / pharmacology
  • Humans
  • Neuronal Plasticity
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiology
  • Psychotropic Drugs / pharmacology*
  • Receptors, Glutamate / metabolism*
  • Synaptic Transmission / drug effects*

Substances

  • Analgesics, Opioid
  • Central Nervous System Stimulants
  • Excitatory Amino Acid Agents
  • Psychotropic Drugs
  • Receptors, Glutamate