Opiate dependence induces network state shifts in the limbic system
Neurobiology of Disease. 2013-11-01; 59: 220-229
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1. Neurobiol Dis. 2013 Nov;59:220-9. doi: 10.1016/j.nbd.2013.07.012. Epub 2013 Jul
Opiate dependence induces network state shifts in the limbic system.
Dejean C(1), Boraud T, Le Moine C.
(1)University of Bordeaux, INCIA, UMR 5287, F-33000 Bordeaux, France; CNRS,
INCIA, UMR 5287, F-33000 Bordeaux, France.
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.
PMID: 23911767 [Indexed for MEDLINE]