Effect Of Antistress Drugs (Alprazolam, Buspirone And Fluoxetine) On Stress Induced Changes Of Brain And Other Organohistopathology In Male Albino Rats

Abstract

Introduction: Stress has an impact to make changes in a range of anatomical, physiological, biological responses consist of psycho-physiological responses. Many studies showed that serum cortisol levels and antioxidant vitamins C and E are a reliable indicator of stress responses in animals. Based on the current available information on exposure to restrained stress standpoint, it was noticed that majority of the studies were centered on their modifications of the immune function rather than the configuration and available reports concerning persuade of antidepressants and reversible assessment after withdrawal on assessment of antistress effects in restrained rats is lacking. Hence, present experimental trials have been designed to examine the consequence of restrained stress and efforts have been directed for studying those novel commonly used antistress drugs viz., alprazolam (benzodiazepine anti-anxiety agent), fluoxetine (a selective serotonin reuptake inhibitor) and buspirone (a non-benzodiazepine anxiolytic drug) to compare for their protective effects in restrained stress 21 days in continuance with stress. While, in contrast, the withdrawal of stress also designed meant for residual 21 days might perhaps counteract or reversible of such restrained stress provoked damage.Materials and Methods: Acclimatized Wistar albino rats weighing about 175 to 225g were obtained for the study and were randomly divided into six grouping of six animals each. Untreated control rats (Group I) reserved uninterrupted in the metabolic cage all through the experimental duration intended for 42 days; Stress induced rats (Group II) were strained daily for 6hrs in wire mesh restrainer intended for 42 days; Group III rats were stressed intended for 21 days by means of observance in mesh restrainer and then retaining animals in normal cages for residual 21 days designed for stress withdrawal and rest of other drug treated groups i.e., groups IV,V and VI rats were stressed intended for 21 days and then treated with alprazolam (5mg/kg body weight, intraperitoneally, BW, IP), buspirone (12mg/kg BW, IP) and fluoxetine drug (20mg/kg BW, IP), respectively for residual 21 days in continuation with stress. All animals were observed daily for mortality and morbidity, physical examinations and clinical observations like general appearance of the animal’s behavior; individual food consumption record of the animals. At the end of the final day subsequent to an overnight fast, all the animals were sacrificed and gravimetrical parameters, relative organ weights, haematological parameters, blood serum cortisol, antioxidant vitamins levels were assessed. Finally, whole brain and relative organs of control and experimental rats were dissected out, blotted free of mucus, weighed to the adjacent milligram and subjected to histopathological evaluations. Results: Results revealed that restrained stress (Group II) being a psychological stress significant (P ≤0.05) change in the food consumption, BWs, gravimetrical parameters, relative organ weights, haematological parameters and serum levels of cortisol and antioxidant vitamins C and E and drugs treated rats. On the other hand, stress withdrawal rats (Group III) and administration of drugs alprazolam (Group III), buspirone (Group III) and fluoxetine (Group III) for residual 21 days in continuance with strain illustrated a remarkable (P≤0.05) improvements by means of neutralizing or recovering of altered parameters while compared to only group II restrained stress induced rats. Histopathological evaluations of stress induced brain sections of cerebral cortex exhibit neuronal cells with indistinct in profile with shrunken intensely stained nuclei, bounded xix

in vacuolated parts, mild focal vacuolar degeneration and there were no features of necrosis, infarcts, inflammation or glial proliferation. Liver sections demonstrated distorted architecture including congestion blood vessels, infiltration, vasodilatation, hydropic, fatty changes and hypertrophy. Kidney sections exhibited mild thickening of tubular basement membrane, focal cloudy swelling of tubular cells and glomerular shrinkage. Testis sections showed atrophic tubules and spermatogenesis did not proceed ahead of pachytene spermatocytes with exhibited signs of degeneration. The Sertoli cells showed vacuolization and intercellular spacing that become wider with occurrence of Leydig cells with shrunken nuclei. However, these histopathological changes were remarkably reversed in stress withdrawal rats (Group III) and neutralized to normal level in stress induced alprazolam (Group IV), buspirone (Group V) and fluoxetine (Group V) drugs treated animals designed meant for remaining 21 days with continuation with stress. Conclusion: Results presented here led us to that, exposure to restrained stress resulted alter the levels of gravimetry, haematological, biochemical parameters and marked histopathological alterations due to peripheral oxidative stress in male albino rats. While, withdrawal of stress or antistress drugs designed meant for residual 21 days in continuance through stress might possibly neutralize restrained stress provoked injure to escorting antioxidant equilibrium and modify hypothalamic-pituitary adrenal (HPA) axis