The Effects Of Adrenoceptor Antagonist Propranolol And Prasozin On Stressed Rats

Objective To explore the effects of adrenoceptor antagonist propranolol and prasozin on the chronic unpredictable mild stress rats' behavioral changes, and serum corticosterone level in rats after being subjected to the acute stress, as well as levels of inducible heat shock protein 70 and inducible nitric oxide synthase, which were expressed in the hippocampus and the prefrontal cortex. To investigate the effects and mechanisms of partial blocks of sympathoadrenomedullary system on stress-induced damages of rats.Methods Thirty-two Wistar male rats were divided randomly into four groups: the control group, the chronic unpredictable mild stress group, the propranolol group and the prasozin group, 8 animals in each. All animals received 21-day chronic unpredictable mild stress with the exception of the controls. Additionally, the propranolol group and the prasozin group animals were treated with intragastric administration of medicines half an hour before stress. Open-field test was adopted to assess behaviors of all animals before and after exposure of the chronic unpredictable mild stress. Thereafter, 6 rats from each group were randomly chosen to be sacrificed by decapitation two hours after the acute stress of 1.0mA, 5s, persisting 60 times. Then, trunk blood was collected, and hippocampus tissue was dissected on a glass plate placed on top of crushed ice and stored at -80℃. And the others were chosen to make paraffin sections of different brain areas. Hematoxylin-eosin staining was used to study morphological changes in the hippocampus and the prefrontal lobe. The content of serum corticosterone was evaluated by cortisol radio-immunoassays, inducible heat shock protein 70 and inducible nitric oxide synthase was measured by western blotting.Results 1. The results of open-field test suggested that the chronic unpredictable mild stress induced significant decreased square crossing numbers, rearing numbers and longer time staying in the central square compared to the controls. Decreased square crossing numbers, rearing numbers and longer time staying in the central square were observed in the propranolol group. There is no statistical difference between the control group and the prasozin group. Compared to the chronic unpredictable mild stress group animals, the propranolol groups exhibited less grooming numbers and stool numbers. Prasozin-administrated groups showed more square crossing numbers and rearing numbers, less time staying in the central square.2. CA3 and dentate gyrus subfields of hippocampus of rats in the chronic unpredictable mild stress group showed decreased number of cell, disturbed cell alignment, increased intercellular space, cell atrophy, and deformity and chromatin condensation. The prefrontal cortex exhibited disturbed cell alignment, increased intercellular space, cell atrophy, and deformity and chromatin condensation. The propranolol rats showed same changes in different brain areas. Damages in CA3 and DG subfields of hippocampus, as well as prefrontal cortex of rats in prasozin group were significant minor compared to that of the chronic unpredictable mild stress rats.3. The levels of serum corticosterone in the propranolol rats and the chronic unpredictable mild stress rats were statistically lower in contrast to the controls. Compared to the chronic unpredictable mild stress group, the propranolol group exhibited no difference in the levels of serum corticosternone, while the prasozin group showed an evident up-regulation of serum corticosterone.4. The levels of HSP70, which were expressed in the hippocampus and the prefrontal cortex of the other groups, all were lower than that of the controls.5. Compared with the controls, propranolol induced an obvious up-regulation of iNOS level both in the hippocampus and the prefrontal cortex. And the exposure of chronic unpredictable mild stress induced an obvious up-regulation of iNOS level only in the hippocampus. Unexpectedly, the level of iNOS in the prefrontal cortex was lower as well, but the difference was statistically insignificant. There was no difference between the control group and the prasozin group. Compared to the chronic unpredictable mild stress group, the propranolol group showed no difference, and statistically down-regulation was observed in the hippocampus of the prasozin rats.Conlusion1.α1-adrenoceptor antagonist prasozin administration can reverse the chronic unpredictable mild stress induced changes of locomotor and exploratory activity, and improve the axoneure morphology significantly, as well as suppress the excessive activity of HPA axis. Moreover, it can help being able to activate the stress response when the chronic unpredictable mild stress rats were subjected to the acute stress. Levels of inducible HSP70 in the hippocampus and the prefrontal cortex were expressed normally, and then iNOS expressions were down-regulated significantly. Accordingly, Prasozin-administrated lessens the damage of brain tissues caused by stress.2.β-adrenoceptor antagonist propranolol administration can relieve the chronic unpredictable mild stress induced anxiety-like behaviors; however, it can't block the chronic unpredictable mild stress induced the changes of locomotor and exploratory activity, and can't improve the axoneure morphology significantly. Further, propranolol exhibits no effect on the activation of stress response. Likewise, it takes no effect on the expressions of inducible HSP70, which can't reduce the increased levels of iNOS induced by stress in the hippocampus and the prefrontal cortex tissues and then produce serious damages in brain.