Related Experiment Video
Updated: May 24, 2026
Animal Models of Depression - Chronic Despair Model (CDM)
Published on: September 23, 2021
5-HT(1A) receptor and apoptosis contribute to interferon-α-induced "depressive-like" behavior in mice
Fengfeng Ping1, Jing Shang, Jia Zhou
1Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Abstract:
Interferon-α (IFN-α)-induced "depressive-like" behavior is a major limitation for the treatment of hepatitis C virus (HCV), especially for patients with psychiatric disorders. Recently, serotonin 1A (5-HT(1A)) receptor and cellular apoptosis are involved in mechanism(s) contributing to depression. To gain insight into this mechanism(s), we used C57BL/6J mice to examine the impact of IFN-α on the modulation of 5-HT(1A) receptor and cellular apoptosis and their relationship. Our results showed that repeated administration of IFN-α (6 MIU/kg, s.c.) induced "depressive-like" behavior of mice in the forced swim test, tail suspension test and sucrose preference test. Besides, the depressive mice exhibited a notable downregulation of 5-HT(1A) receptor and upregulation of cleaved caspase-3 and Bax/Bcl-2 ratio. These changes could be blocked by the 5-HT(1A) receptor agonist 8-OH-DPAT (0.5 mg/kg, i.p., 30 min before IFN-α administration), but not by the standard antidepressant imipramine (10 mg/kg, i.p., 30 min before IFN-α administration) although both of them could ameliorate the depressive-like behavior of mice. These findings indicated that repeated injection with IFN-α provoked "depressive-like" behavior through cellular apoptosis, which could be ameliorated by the activation of 5-HT(1A) receptor.
Insights
Interferon-alfa (IFN-α) causes depressive-like behavior by downregulating serotonin 1A (5-HT1A) receptors and increasing cellular apoptosis. Activating 5-HT1A receptors can alleviate these effects.
Area of Science:
- Neuroscience
- Pharmacology
- Hepatology
Background:
- Hepatitis C virus (HCV) treatment with Interferon-alfa (IFN-α) can induce depressive-like behaviors, limiting its therapeutic use, particularly in patients with pre-existing psychiatric conditions.
- Serotonin 1A (5-HT1A) receptors and cellular apoptosis are implicated in the mechanisms underlying depression.
Purpose of the Study:
- To investigate the impact of IFN-α on 5-HT1A receptor modulation and cellular apoptosis in mice.
- To explore the relationship between IFN-α-induced depressive-like behavior, 5-HT1A receptor function, and apoptosis.
Main Methods:
- C57BL/6J mice were administered IFN-α to induce "depressive-like" behavior.
- Behavioral tests included the forced swim test, tail suspension test, and sucrose preference test.
- Changes in 5-HT1A receptor expression, cleaved caspase-3, and Bax/Bcl-2 ratio were analyzed. The effects of 5-HT1A receptor agonist 8-OH-DPAT and imipramine were evaluated.
Main Results:
- IFN-α administration induced "depressive-like" behavior in mice.
- Depressive mice showed downregulated 5-HT1A receptors and upregulated cleaved caspase-3 and Bax/Bcl-2 ratio, indicating increased cellular apoptosis.
- The 5-HT1A receptor agonist 8-OH-DPAT blocked these molecular changes and ameliorated depressive-like behavior, while imipramine only ameliorated behavior.
Conclusions:
- Repeated IFN-α injections provoke "depressive-like" behavior in mice, mediated by cellular apoptosis.
- Activation of the 5-HT1A receptor pathway is a key mechanism in mitigating IFN-α-induced depression.
- Targeting 5-HT1A receptors may offer a therapeutic strategy for IFN-α-associated depression in HCV patients.
