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Arzneimittelforschung 2010; 60(3): 109-115
DOI: 10.1055/s-0031-1296258
CNS-active Drugs · Hypnotics · Psychotropics · Sedatives
Editio Cantor Verlag Aulendorf (Germany)

Differential involvement of 5-HT1A and 5-HT1B/1D receptors in human interferon-alpha-induced immobility in the mouse forced swimming test

Hongmei Zhang
1   Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Wei Wang
1   Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Zhenzhou Jiang
1   Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Jing Shang
1   Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
,
Luyong Zhang
1   Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China
› Author Affiliations
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Publication History

Publication Date:
02 December 2011 (online)

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Abstract

Although Interferon-alpha (IFN-α, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuro-psychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT1A receptor-and 5-HT1B receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT1A receptor- and 5-HT1B receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-α-induced increase of the immobility time in the forced swimming test; (2) 5-HT1A receptor- and 5-HT1B receptor ligands alone or in combination had no effects on IFN-α-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT1A receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT1A receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-α-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT1B receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT1B/1D receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-α-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-α-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to the 5-HT1B receptor, the 5-HT1A receptor signal plays the dominant role in improving the anti-immobility effect of fluoxetine in the IFN-α-induced depression; (2) combination of the 5-HT1A antagonist with subactive fluoxetine can be helpful in IFN-α-induced depression treatment.

Key words

CAS 9008-11-1 - Depression - Forced swimming test - Interferon-alpha - 5-HT1A receptor - 5-HT1B receptor