This project examines the physiological effects and the underlying biochemical mechanisms of the action of delta opioid peptide DADLE in cell survival. In this fiscal year, we found that DADLE enhances the survival of rat embryonic dopaminergic neurons in vitro and in vivo. Embryonic dopaminergic cells pretreated with DADLE promote the survival of those cells when transplanted into the 6-OHDA lesioned rats. In the methamphetamine (METH) studies, we found that administration of a single high dose of METH (25 mg/kg, i.p.) was able to cause a near complete depletion of striatal dopamine and a close to 50% loss of dopamine transporters (DAT) and tyrosine hydroxylase (TH)at the striatum. A single administration of DADLE (20 mg/kg, i.p.), given 30 min before METH, completely blocked the loss of DAT and TH, and partially blocked the depletion of dopamine caused by METH. The gene expression of a tumor necrosis factor p53 affected by METH was also blocked by DADLE. Finally, we found that DADLE can prevent the the functional loss of DAT and TH caused by METH. Thus, endogenous opioid peptide may play important role in cell survival against neurotoxicity caused by certain psychostimulants and neurotoxic agents.
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