WITHDRAWN: Modulation of CUMS Induced Behaviour Deficits in Rats by Alpha Lipoic Acid: Possible Involvement of Dopaminergic and Serotonergic Neurotransmission

Abstract

Purpose: Stress is an important factor having a high impact on psychological development which alters emotion, cognition and related behavioural outputs. Alpha lipoic acid (ALA) is a potent neuroprotectant and antioxidant; however, it has not been studied in clinically relevant, chronic unpredictable mild stress (CUMS) induced behaviour deficits model in rats as well as its mechanism of action is unclear. Hence, the purpose of this study was to determine its antidepressant activity in CUMS induced depression-like behaviour and to understand its mechanism of action using brain monoamine estimations and molecular docking study.Methods: The Wistar rats were divided into 6 groups. Group I vehicle control (without stress), Group II- CUMS, Group III- fluoxetine (FLX) (50 mg/kg), Group IV, V, and VI were treated with ALA (50, 100, 200 mg/kg, p.o.) respectively. All the groups, except I, were subjected to CUMS along with the treatments which were given orally from day 1 to day 42. The behavioural parameters like sucrose preference test (SPT), Morris water maze (MWM), resident intruder test (RIT), marble-burying test (MBT) were performed on day 0, day 21, and day 42 and forced swim test (FST) on day 42 only. Animals were sacrificed at the end of the study; the brain homogenate was prepared and used for the antioxidant, histopathology and monoamine estimations.Results: When compared with CUMS group, ALA (50, 100, 200) treatment displays improved behavioural parameters, increased GSH, SOD, catalase and reduced MDA, NO. Concentrations of monoamines (5-HT, DA, NE) were also found to be restored in brain homogenate. Histopathological results indicated the protection of CA3 neurons in the hippocampus. Computational molecular docking revealed strong binding of ALA on the 5HT3 receptor. Conclusion: Consequently, the study demonstrates that ALA might be exhibiting antidepressant effects in part by restoring monoamines as well as may be modulating the 5HT3 receptor.