Opiate dependence induces network state shifts in the limbic system

Neurobiol Dis. 2013 Nov;59:220-9. doi: 10.1016/j.nbd.2013.07.012. Epub 2013 Jul 30.


Among current theories of addiction, hedonic homeostasis dysregulation predicts that the brain reward systems, particularly the mesolimbic dopamine system, switch from a physiological state to a new "set point." In opiate addiction, evidence show that the dopamine system principal targets, prefrontal cortex (PFC), nucleus accumbens (NAC) and basolateral amygdala complex (BLA) also adapt to repeated drug stimulation. Here we investigated the impact of chronic morphine on the dynamics of the network of these three interconnected structures. For that purpose we performed simultaneous electrophysiological recordings in freely-moving rats subcutaneously implanted with continuous-release morphine pellets. Chronic morphine produced a shift in the network state underpinned by changes in Delta and Gamma oscillations in the LFP of PFC, NAC and BLA, in correlation to behavioral changes. However despite continuous stimulation by the drug, an apparent normalization of the network activity and state occurred after 2 days indicating large scale adaptations. Blockade of μ opioid receptors was nonetheless sufficient to disrupt this acquired new stability in morphine-dependent animals. In line with the homeostatic dysregulation theory of addiction, our study provides original direct evidence that the PFC-NAC-BLA network of the dependent brain is characterized by a de novo balance for which the drug of abuse becomes the main contributor.

Keywords: Addiction; Allostasis; Delta; Electrophysiology; Gamma; Homeostasis; LFP; Morphine; Naloxone; Opiate; Oscillations; Synchronization; Theta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Amygdala / drug effects
  • Amygdala / physiopathology
  • Animals
  • Brain Waves / drug effects*
  • Brain Waves / physiology
  • Disease Models, Animal
  • Limbic System / drug effects
  • Limbic System / physiopathology*
  • Male
  • Morphine / adverse effects
  • Motor Activity / drug effects
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Narcotics / adverse effects
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / physiopathology
  • Opioid-Related Disorders / pathology*
  • Opioid-Related Disorders / physiopathology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Wakefulness


  • Narcotic Antagonists
  • Narcotics
  • Naloxone
  • Morphine