EN
Biphalin is a dimeric opioid peptide, that exhibits a high affi nity for all three opioid receptors types (miu, delta and kappa). When administered intracerebroventricularly it has been shown to be more potent than morphine and ethorphine at eliciting antinociception. Biphalin is currently undergoing intensive preclinical study. It is recognized in recent years that activation of delta-opioid receptor elicits neuroprotection against hypoxia and ischemia, but the underlying mechanisms are not fully understood. In this study we tested the effect of biphalin and the inhibition of opioid receptors by naltrexon (Ntx) on survival of neurons in rat organotypic hippocampal culture challenged with NMDA in vitro. Cell survival was estimated with fl uorescent cell-death marker propidium iodide. Our main fi ndings are that (1) biphalin in the concentration of 100 μM reduces NMDA-induced neuronal damage; (2) biphalin neuroprotective effect is abolished by opioid receptors antagonist naltrexon; (3) naltrexon by itself does not change NMDA-induced neuronal damage; (4) reduced number of dead cells was clearly shown even when biphalin was applied with a delay after NMDA challenge. These results demonstrate that biphalin, multireceptor opioid peptide, can reduce NMDA-induced neuronal damage. This work was supported by MSHE Polish Mitochondrial Network grant.