Anxiolytic and antidepressant properties of methylene blue in animal models.

Methylene blue (MB) has been intermittently used in manic depressive illness over the past century. However, to our knowledge, it has not been studied in the behavioural animal models. The present study was designed to evaluate whether the intravenous (i.v.) administration of MB in a dose range of 1.87-60 mg kg-1 would affect the performance of rats in the elevated plus-maze and the forced swimming (FST) tests. In the plus-maze, MB in doses ranging from 3.25 to 30 mg kg-1 significantly increased the percentage of open arm entries and exhibited an inverted U-shaped dose-response curve. Over a dose range, 7.5-30 mg kg-1, MB also increased time spent in open arms. These data suggest that MB has anxiolytic properties. On the other hand, MB, at doses of 15 and 30 mg kg-1 significantly decreased the immobility time in the FST and behaved as an antidepressant compound in these doses. As known, MB has prominent effects on the nitrergic system; Nitric oxide (NO) produced from L-arginine by the enzyme NO-synthase (NOS) activates soluble guanylyl cyclase (sGC) and exerts its effects on tissues through cGMP. MB acts as a direct inhibitor of NOS as well as of sGC. It also inactivates NO extracellularly through generation of superoxide anions. Thus, it can be speculated that NOS-NO-cGMP pathway may be involved in the antidepressant and anxiolytic actions of MB, and this may lead to search for new antidepressant and anxiolytic compounds.