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Opioid withdrawal activates MAP kinase in locus coeruleus neurons in morphine‐dependent rats in vivo
Author(s) -
Schulz Stefan,
Höllt Volker
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00103.x
Subject(s) - locus coeruleus , mapk/erk pathway , opioid , opioid receptor , neuroscience , protein kinase a , opioid peptide , kinase , (+) naloxone , in vivo , phosphorylation , microbiology and biotechnology , chemistry , endocrinology , receptor , biology , medicine , central nervous system
Opioid dependence is widely believed to result from neuroadaptations in specific brain regions. However, the precise molecular mechanisms underlying these adaptations are not yet clear. Our aim was to explore the role of mitogen‐activated protein kinase (MAPK) in μ opioid receptor signalling in vivo . Using anti‐phospho MAPK antibodies, activated MAPK was detected in cortical neurons (layers II/III), median eminence, amygdaloid and hypothalamic nuclei in untreated animals. Dense nuclear and cytoplasmic staining was observed resulting in full visualization of processes in these cells. Chronic, but not acute, administration of morphine greatly diminished this staining pattern while μ opioid receptor levels and levels of MAPkinase as detected with a phosphorylation state‐independent antibody were unchanged. When opioid withdrawal was precipitated with naloxone a dramatic increase in MAPkinase phosphorylation was observed in somata and fibres of locus coeruleus, solitary tract and hypothalamic neurons. Thus, the differential activation state of MAPK could have important implications for understanding the mechanisms underlying opioid tolerance and dependence.