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Volume 12, Issue 1
  • ISSN: 2211-5560
  • E-ISSN: 2211-5579

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 metformin-treated 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 an increase in hippocampal 5-HT levels and 5-HT-1A heteroreceptor expression.

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2025-03-13

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Hippocampal Serotonin and Responses to Immobilization Stress in Rats Treated with Metformin
Current Psychopharmacology 12, E290424229519 (2024); https://doi.org/10.2174/0122115560289942240427041345
/content/journals/cpsp/10.2174/0122115560289942240427041345
/content/journals/cpsp/10.2174/0122115560289942240427041345
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  • Article Type:     Research Article
Keyword(s): 5-HT-1A; anxiety; hippocampus; immobilization stress; Metformin; serotonin

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