Neural Pathway Between The Nucleus Accumbens And The Rostral Ventrolateral Medulla In Anorexia Nervosa Model Rats

Objective: This study was designed to investigate the potential neural pathways connecting nucleus accumbens(NAc)and rostral ventrolateral medulla(RVLM),which was involved in the central regulation of cardiovascular function of model rats with anorexia nervosa(AN).This study provides a theoretical basis for stating the central regulatory mechanism of cardiovascular function of patients with AN.Methods: Adult male Sprague Dawley(SD)rats had been adaptive feeding for a oneweek habituation period.The AN rat model was established following the simulation method of diet and exercise after 21 days.And the body weight of the rats was measured daily,when the body weight of model rats was lower than 25% of the body weight of the normal-fed rats,and the comparison between the groups had statistical difference,it can be regarded that the modeling was successful.The discharges of RVLM neurons and peripheral cardiovascular function indicators in control and model rats were recorded by using Powerlab multi-channel recording technique at the same time.To investigate whether NAc neurons directly project to the RVLM,microinjection of the retrograde tracer,FluoroGold(FG),was performed in the sites of the RVLM of control and AN model rats.Then FG-labeled neurons in target regions were examined with a fluorescent inverted microscope.By electrically stimulating the NAc nucleus in normal and model groups of rats,statistical analysis was performed on the RVLM neuron firing activity and changes in peripheral physiological indicators after electrical stimulation in the two groups of rats to determine whether there is a functional connection between NAc and RVLM.Results: 1.Changes in body weight of AN model rats before and after modelingThe weight data of rats in the control group and the AN model group were recorded on time every day.After the 3 weeks of model preparation time,rats of the restricted feeding group demonstrated a significant body weight reduction compared with that of the control animals.The body weight of model rats was lower than 25% of the body weight of control rats,and the difference between the two groups was statistically significant(P<0.05),demonstrating the successful establishment of AN model.2.Monitoring cardiovascular responses and neuronal activity of the RVLM in AN model ratsThe systolic blood pressure(SBP),mean arterial pressure(MAP)and heart rate(HR)of AN group were dramatically reduced,and the discharge frequency of RVLM neurons was significantly increased,in comparison with that of control group.3.Morphological connection between NAc and RVLMA 0.5 ?L saline solution consisting of 4 % FG was subsequently injected at the RVLM site in control and model group rats.After injection of FG into the RVLM nucleus,retrograde fluorescent gold-labeled neuron distribution in the paraventricular nucleus(PVN)and NAc nucleus can be observed with a fluorescent inverted microscope.4.Functional connection of NAc and RVLMIn normal rats,we observed that SBP was lowered(P<0.05)following the stimulation of 200?A current and remarkably decreased following another stimulation of 400?A current(P<0.01).Besides,the HR of normal rats was significantly decreased(P<0.05),while the discharge frequency of the RVLM neurons was significantly raised(P<0.01)in response to the 400?A current stimulation.In addition,the activities in response to stimulation in AN model rats were also observed.It's noteworthy that a strong relationship between these activities and the stimulation of 400?A current was observed.More specifically,both SBP and the HR were significantly reduced(P<0.05)while the discharge frequency of RVLM neurons significantly increased(P<0.05).After 400?A stimulation,compared with the normal rats,the diastolic blood pressure(DBP)and MAP of model rats were remarkably reduced(P<0.05),and the discharge frequency of RVLM neurons in AN model rats tended to increase.Conclusion: A rat model of AN was successfully established using hyperactivity and restricted feeding.More important,a neural connecting between NAc and RVLM was observed,showing that this pathway might involve in the regulation of cardiovascular function in AN model rats.