Does acupuncture response increase with the increasing dosage: A preclinical study investigating rats with sleep deprivation

Abstract

BackgroundThe effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials. However, whether higher dosage (more frequent) acupuncture can bring greater responses (a greater size of effect) is less understood. ObjectiveThis study is designed to investigate whether a five-times weekly (5 Ts/w) electroacupuncture (EA) treatment is better than a three-times weekly (3 Ts/w) EA in alleviating sleep deprivation, and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral tests. MethodsForty-six male Sprague-Dawley rats were randomly divided into control group (n = 10), model group (n = 12), EA-3 Ts/w group (n = 12), and EA-5 Ts/w group (n = 12). Except for the control group, the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology. Then, rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy, respectively. After modeling and interventions, all four groups received four behavioral tests as follows: (1) sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System (CLAMS). (2) Cognitive functions were assessed by Novel Object Recognition (NOR) test. (3) Depressive-like behaviors was evaluated by Open-Field (OF) test. (4) Anxiety-like behaviors was appraised by Elevated Plus-Maze (EPM) test. After finishing the behavioral tests, the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope. Results(1) CLAMS: two EA groups derived more sleep time within 24 h than the model group (both P<0.05), and no statistical differences was found between these two EA groups (P>0.05). (2) NOR test: NOR ratio in the EA-3 Ts/w group was higher than that of the model group (P<0.05) but lower than that of either the control group (P<0.05) or the EA-5 Ts/w group (P<0.05). (3) OF test: the difference of horizontal movements between the EA-3 Ts/w group and the EA-5 Ts/w group was not significant (P>0.05), although both of them were lower than that of the control group (both P<0.05) but higher than that of the model group (P<0.05). (4) EPM test: no significant decline of open-arm total time (OT) was found in EA-3Ts/w group (P>0.05) but was found in both the model group (P<0.05) and the EA-5Ts/w group (P<0.05) compared to the control group. Conclusion(1) Five-week EA treatment can partially mitigate cognitive dysfunctions, anxiety-like behaviors, and depressive behaviors in rats with sleep deprivation, and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons. (2) There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats. (3) 5 Ts/w EA treatment might be more effective than 3Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat's anxiety-like behaviors at the same time.