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Effect of Opioids on Integrity of White Matter
Author(s) -
Korneeva Nadejda L,
Fan Ruping,
Schrott Lisa M,
Arnold Thomas,
Graham Derrel
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.926.8
Subject(s) - oxycodone , opioid , pharmacology , nucleus accumbens , morphine , medicine , heroin , analgesic , neuropathic pain , neuroscience , anesthesia , receptor , psychology , drug
Oxycodone (6‐deoxy‐7,8‐dehydro‐14‐hydroxy‐3‐O‐methyl‐6‐oxomorphine) is a strong semi‐synthetic opioid. It is prescribed to treat different types of pain especially when other opioids are ineffective. Oxycodone has close structural similarity to morphine and heroin and binds not only m‐ but also k‐opioid receptors. Unfortunately, similar to other opioids, repetitive oxycodone administration has the potential to develop analgesic tolerance, withdrawal, and addiction. Recently, another concern regarding the effect of chronic or over‐dose opioid exposure has emerged: their effect on neuronal degeneration. Leukoencephalopathy or damage of white matter has been described as one of the effects that heroin abusers develop, and was recently documented in a patient after morphine and oxycodone administration. The exact mechanisms underlying the neurotoxic effect of opioids on the Central Nervous System are still not fully understood. To investigate the effect of opioid treatment on rat white matter we used an animal model in which female rats were gavaged with 15 mg/kg oxycodone every 24 hours for 30 days. In our study we observed that chronic oxycodone exposure induces oxidative/nitrosidative stresses in three brain areas in rats: nucleus accumbens, cortex and brain stem. We demonstrated activation of pro‐apoptotic machinery in rat brains after oxycodone treatment. Interestingly, activated caspase 3 was predominantly localized in areas containing white matter suggesting increased axonal damages after chronic oxycodone exposure. The increased level of a‐synuclein aggregates and amyloid precursor protein (APP) in oxycodone‐exposed cerebellum confirmed the axonal injury. We also demonstrated induction of pro‐apoptotic protein Bax by oxycodone, morphine and DAMGO in breast carcinoma cells MCF7, which are known to express the m‐opioid receptor. Support or Funding Information LMS was supported by Grant No. 2R01GM20818 from the National Institute of General Medical Sciences.