ABSTRACT
Objective To investigate the effects of Oxytocin(OT) on hippocampal long-term potentiation(LTP) and FOS protein expression induced by peripheral stimulation.Methods Single stimulation pulses were delivered to the left sciatic nerves to evoke the field excitatory postsynaptic potentials (fEPSPs) in the right hippocampal CA1. Tetanic stimulation was used to induce hippocampal LTP. Different groups of rat were given NS,OT,Oxytocin antagonist-Atosiban + OT before tetanic stimulation,into lateral ventricle(LV) respectively. Expression of FOS protein was compared among the groups by histopathological and immunohistochemistry. Results Single stimulation evoked fEPSPs in hippocampal CA1,which average latency was (171.9?33.1)ms and average amplitude was (25.7?8.4)?V. Tetanic stimulation induced hippocampal LTP and increased the expression of FOS protein. Intracerebroventricular injection of OT inhibited hippocampal LTP and decreased the expression of FOS protein. This effect of OT was blocked by the pretreatment with Atosiban. Conclusion The results suggested that OT may play an inhibitory role in leaning and memory of rats and the effect is mediated by OT receptor.
ABSTRACT
OBJECTIVE: Oxytocin antagonists maybe useful in inhibiting the uterine contractions of preterm labor. One such compound is TT-235. The purpose of this study was to compare the resistance of TT-235 and oxytocin to enzymatic degradation by oxytocinase in pregnant human. METHODS: Blood samples from pregnant women not in labor were incubated in vitro with known amounts of oxytocin and TT-235. Samples were collected at 0, 15, 30, 45 and 60 minute intervals for oxytocin analysis and at 0, 10, 60 and 360 minutes for TT-235 analysis. Oxytocin was analyzed by radioimmunoassay after extraction while TT-235 was analyzed by radioreceptor assay. RESULTS: In human blood, oxytocin was readily metabolized with greater than 83% disappearance over the 60 minute incubation period. In contrast, TT-235 was stable up to 360 minutes of incubation. CONCLUSION: This study suggests that: (1) blood from pregnant human does contain oxytocinase at least in vitro; and (2) TT-235 was resistant to enzymatic degradation by human blood, implying that this oxytocin antagonist may have prolonged activity in vivo in humans.