On the Effect of Minocycline on the Depressive-Like Behavior of Mice Repeatedly Exposed to Malathion: Interaction Between Nitric Oxide and Cholinergic System Publisher Pubmed



Saeedi Saravi SS^{1, 2, 3} ; Amirkhanloo R⁴ ; Arefidoust A^{1, 2} ; Yaftian R^{1, 2} ; Saeedi Saravi SS^{1, 2, 3} ; Shokrzadeh M⁴ ; Dehpour AR^{1, 2} Show Affiliations
Source: Metabolic Brain Disease Published:2016

Abstract

This study was performed to investigate the antidepressant-like effect of minocycline in mice exposed to organophosphate pesticide malathion and possible involvement of nitric oxide/cGMP pathway in this paradigm. Mice were administered specific doses of malathion once daily for 7 consecutive days. After induction of depression, different doses of minocycline were daily injected alone or combined with non-specific NOS inhibitor, L-NAME, specific inducible NOS inhibitor, AG, NO precursor, L-arginine, and PDE5I, sildenafil. After locomotion assessment in open-field test, immobility times were recorded in the FST and TST. Moreover, hippocampal nitrite concentrations and acetylcholinesterase activity were measured. The results showed that repeated exposure to malathion induces depressive-like behavior at dose of 250 mg/kg. Minocycline (160 mg/kg) significantly reduced immobility times in FST and TST (P < 0.001). Combination of sub-effective doses of minocycline (80 mg/kg) with either L-NAME (3 mg/kg) or AG (25 mg/kg) significantly exerted a robust antidepressant-like effect in FST and TST (P < 0.001). Furthermore, minocycline at the same dose which has antidepressant-like effect, significantly reduced hippocampal nitrite concentration. The investigation indicates the essential role for NO/cGMP pathway in malathion-induced depressive-like behavior and antidepressant-like effect of minocycline. Moreover, the interaction between nitrergic and cholinergic systems are suggested to be involved in malathion-induced depression. © 2015, Springer Science+Business Media New York.