Hippocampal Serotonin and Responses to Immobilization Stress in Rats Treated with Metformin

Title:Hippocampal Serotonin and Responses to Immobilization Stress in Rats Treated with Metformin

Volume: 12

Author(s): Rushda Afroz*, Tabinda Salman, Shazia Nawaz, Nazish Mustafa, Munnum Zafar and Darakhshan Jabeen Haleem

Affiliation:

• Neuroscience Research Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

Abstract:

Background: Stress-related illnesses and depression are rising in modern society. Selective serotonin reuptake inhibitors as well as other antidepressants, are also not very effective and commonly exhibit partial remission, suggesting the need for novel therapeutic agents for treating anxiety and depression.

Objective: The present study was designed to investigate serotonergic mechanisms in the potential anxiolytic and stress-reducing effects of metformin.

Method: In the first experiment, rats were given two doses (50 and 100 mg/kg) of metformin to monitor the effects of repeated administration on motor activity, anxiety, and 5-HT-1A receptor expression in the hippocampus and raphe nuclei. The second experiment was conducted in 2 parts, in 2a. experiment, control, and metformin (50 mg/kg) treated rats were immobilized for 2 hours for 5 consecutive days. Food intake and body weight were monitored daily and anxiety-like behavior was monitored on days 2 and 6. On day 6, rats were again immobilized for 2 hours, and after termination of stress rats were sacrificed to collect the hippocampus for HPLC-EC analysis of serotonin (5-hydroxytryptamine; 5-HT) and 5-hydroxy indole acetic acid (5-HIAA). In 2b. experiment, control, and metformin (50 mg/kg) treated rats were immobilized for 2 hours, and after 2 hours rats were sacrificed to collect the hippocampus for HPLC-EC analysis of 5-HT and 5-HIAA.

Results: We found that metformin treatment exhibited anxiety reduction associated with greater expression of 5-HT-1A receptor in the hippocampus and reduced expression in the raphe nuclei. Immobilization stress-induced food intake and body weight deficits were comparable in control and metformin-treated rats, but the anxiogenic effects of stress were smaller in the metformintreated group. Stress-induced decreases of hippocampal 5-HT were smaller in metformin-treated than in control rats.

Conclusion: Metformin can reduce stress-induced anxiety mediated via an increase in hippocampal 5-HT levels and 5-HT-1A heteroreceptor expression.

Cite this article as:

Afroz Rushda*, Salman Tabinda, Nawaz Shazia, Mustafa Nazish, Zafar Munnum and Haleem Jabeen Darakhshan, Hippocampal Serotonin and Responses to Immobilization Stress in Rats Treated with Metformin, Current Psychopharmacology 2024; 12 : e290424229519 . https://dx.doi.org/10.2174/0122115560289942240427041345

DOI https://dx.doi.org/10.2174/0122115560289942240427041345	Print ISSN 2211-5560
Publisher Name Bentham Science Publisher	Online ISSN 2211-5579