Antidepressant-like effect of minocycline in mice forced swimming test: minor involvement of the noradrenergic system

Abstract

Introduction: Minocycline is a tetracycline antibiotic drug that is receiving attention as an alternative for the treatment of depression. Several mechanisms have been proposed for this effect. The current study evaluated the involvement of the noradrenergic system on the antidepressant-like effect of minocycline. Methods: The total immobility time was evaluated as an index of depression in mice forced swimming test (FST). Minocycline (40 mg/kg) was injected for 3 days. Imipramine (5 mg/kg, a tricyclic antidepressant), prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist), propranolol (2 mg/kg, a β-adrenoceptor antagonist) were injected 30 min before the last dose of minocycline, α-methyl-p-tyrosine (100 mg/kg, an inhibitor of tyrosine hydroxylase) was administered 4 hours before minocycline final dose. 
Results: Minocycline decreased the immobility time during FST. The injection of prazosin prevented the anti-depressant like effect of minocycline. While, imipramine, yohimbine or propranolol potentiate the anti-depressant like effect of minocycline during the FST. Besides that, the pretreatment of mice with α-methyl-p-tyrosine did not change the minocycline antidepressant-like effect in the FST. 
Conclusion: The present study suggests that the noradrenergic system has a trivial role in the antidepressant-like effect of minocycline, the impact on neuroinflammation and cytokines might be more important.