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
Keywords:
Metformin, anxiety, immobilization stress, serotonin, 5-HT-1A, hippocampus.
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.
