The Histologic Effect of Baclofen in Rat’s brain: An Experimental Study

Abstract

Background: Baclofen is the only clinically available metabotropic GABABreceptor agonist. Several reports have been discussed the efficacy of baclofen but theavailable data on its effect on behavior and brains' histology are still limited.Objectives: This work aims to assess the effects of long term exposure to baclofen(8weeks) on behavior and brains' histology in ratsMethods: Analysis of data of Twenty five healthy male Albino rats were performed.Rats weighing about 200–210 g with a mean age of 65 days were randomly selectedand categorized into three groups: Group 1(LD50 group): included five rats thatgavaged with a single dose of baclofen to test the LD50 of the drug (145mg per Kg).Group 2. (control group): included eight rats were gavaged with distilled water for2 months. Group 3. (baclofen group): included 12 rats gavaged with 15mg/kg ofbaclofen (1/10th LD50) for 2 months. Behavioral Tests were conducted on all animalsin groups 2 and 3 including Open-field test, Open -field habituation task, and objectrecognition(Novel) to examine the influence of drugs on the cognition of rats. Allanimals were euthanized with ether after 24hours of the last day of treatment. Brainswere excised and collected from rats of groups 2 and 3.Fixation of tissues was doneusing a buffered solution of ten percent of formalin for twenty-four hours with paraffinwax embedding. Sectioning and staining by hematoxylin and eosin protocol (H&E)and prepared to be examined histologically. To differentiate between the data of group2 and 3 , statistical analysis was performed by 1- way analysis of variance (ANOVA).Least significant difference test with the Duncan test was used. Value of P of equal orless than 0.05 means the difference is significant.Results: This study revealed that the rats of the baclofen group traveled a greater totaldistance(in both sessions) when compared with those of control indicating theirhyperactivity. The zone-specific analysis showed that the rats that were administeredwith baclofen consumed markedly greater time nearby the walls in the peripheralReceived5.11.2020Accepted15.11.20202part in the arena throughout the first and 2nd 15- min session in comparison withthose of the control group indicating the generalized hyperactivity and exploration. Ratsof control group preferred the novel object in comparison with those of baclofengroup. However, there is no marked difference in the index of discrimination amongrats of groups 2 and 3. Histological sections of rats’ brains in the group that wereadministered with 15mg/kg of baclofen for 2 months ( baclofen group) revealed adiminished thickness in the pyramidal cells’ layer, irregular faintly stained cells withshrinkage in some pyramidal nerve cells, dark staining cytoplasm, and losing thecharacteristics of their nuclei.Conclusions: Chronic administration with baclofen (15mg/kg/day/2months) induceschanges in the brain histology in rats, however, baclofen has no adverse effect onthe behavior. To the best of our information, our work is the 1st that focuses on theinfluence of baclofen on both the behavior and the brains' histology. Our data suggestingthat baclofen may have clinical utility