RRC ID 48549
Author Matsushita Y, Omotuyi IO, Mukae T, Ueda H.
Title Microglia activation precedes the anti-opioid BDNF and NMDA receptor mechanisms underlying morphine analgesic tolerance.
Journal Curr Pharm Des
Abstract Herein, we investigated the role of periaqueductal gray (PAG)-resident microglia in the development of morphine tolerance and its underlying mechanisms. We showed that clodronate and minocycline known as microglia inhibitors reversed morphine tolerance, providing proof that microglia activation has key role in the development of morphine tolerance. The microglia-mediated anti-opioid mechanism occurs via sequential BDNF release and NMDA expression. Experimental evidence is provided here as conditional bdnf knockout mice (bdnf⁻/⁻) failed to develop tolerance following Cre-recombinase adenovirus treatment. Increased BDNF expression followed microglia activation in acute minocycline treatment reversible manner. Following BDNF release, NR2A subunit of NMDA receptor was upregulated in anti-BDNF reversible manner showing the contribution of BDNF signaling in the control of NMDA receptor expression following chronic morphine treatment. Our data provide compelling evidence that microglia activation and BDNF release are key regulators in opioid tolerance mechanism via glutaminergic synapse plasticity.
Volume 19(42)
Pages 7355-61
Published 2013-1-1
DOI 10.2174/138161281942140105161733
PII CPD-EPUB-20130219-38
PMID 23448475
MeSH Analgesics, Opioid / pharmacology* Animals Blotting, Western Brain-Derived Neurotrophic Factor / metabolism* Male Mice Mice, Inbred C57BL Microglia / drug effects* Morphine / pharmacology* Phagocytosis / drug effects Receptors, N-Methyl-D-Aspartate / metabolism*
IF 2.208
Times Cited 17
DNA material AxCANCre (RDB01748)