This project examines the physiological effects and the underlying biochemical mechanisms of the action of delta opioid peptide DADLE in cellular survival. Neurotrophic factors, including the nerve growth factor (NGF), are known to play important roles in the development and survival of neurons. Opioids have been known to affect neuronal development. Thus, there were reports that opioid agonists and antagonists regulate NGF levels in the neonatal rodent brain. For example, opioid antagonist naltrexone increased the level of NGF in the striatum of neonatal rats. On the other hand, the opioid agonists like methadone and buprenorphine were reported to reduce the level of NGF in the striatum of newborn rats. However, to our knowledge, the effect of opioids on NGF levels in the brain of adult animals has never been reported. Thus, because DADLE is neuroprotective in adult animals and because neurotrophic factors are neuroprotective in the brain, we examined if DADLE may affect the level of neurotrophic factors including NGF and GDNF in adult CD-1 mice. Here we found that chronic treatment of DADLE caused a significant increase of nerve growth factor (NGF) in the hippocampus and the mid-brain of adult albino Swiss (CD-1) mice, but not in the striatum or frontal cortex. The glia-derived neurotrophic factor (GDNF) was not significantly affected. Thus, the neuroprotective action of DADLE may be mediated in part by NGF.
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