Anxiolytic-like effect of linezolid in experimental mouse models of anxiety

Linezolid, an oxazolidinone class antibiotic is a reversible and nonselective inhibitor of monoamine oxidase (MAO) enzyme, mainly for MAO-A subtype. Its antidepressant-like effect has been previously demonstrated in the rodent models of depression. MAO-A enzyme has been shown to play a role in the pathophysiology of anxiety disorders and inhibition of MAO-A in the brain could be used to treat anxiety disorders. Thus, the objective of this study was to investigate the putative anxiolytic effects of linezolid in rodent models of anxiety. Mice were acutely injected with linezolid (5-40 mg/kg, i.p.), diazepam (2 mg/kg, i.p.) and moclobemide (10 mg/kg., i.p.). Linezolid (20 and 40 mg/kg), diazepam and moclobemide significantly (p<0.05) increased the percentage of time spent and entries into open arms in the elevated plus maze (EPM) test without altering the closed arm entries. Linezolid (10-40 mg/kg) significantly (p<0.05) increased the latency time to leave the light compartment, linezolid (20 and 40 mg/kg) significantly (p<0.05) increased total time spent in light compartment and linezolid (40 mg/kg) significantly (p<0.05) increased the number of transition between compartments in the light/dark (L/D) aversion test. Moreover, diazepam and moclobemide also showed significant (p<0.05) effects on all parameters in the (L/D) test. In addition, linezolid (20 and 40 mg/kg), diazepam and moclobemide significantly (p<0.05) increased the number of and time spent in head dipping, whereas significantly (p<0.05) decreased the head dipping latency in hole board (HB) test. In the present study linezolid at higher doses (20 and 40 mg/kg), diazepam and moclobemide showed more pronounced anxiolytic effects as compared to lower doses of linezolid (5 and 10 mg/kg). Whereas, the effects of linezolid at higher doses, diazepam and moclobemide on mice behavior in anxiety models was found quite similar. In conclusion, these results verified, for the first time, the anxiolytic properties of linezolid and suggest that linezolid may be considered an alternative approach for the management of anxiety disorders.