Anxiolytic effect of methylene blue microinjected into the dorsal periaqueductal gray matter

Abstract

The dorsal periaqueductal gray (DPAG) has been implicated in the behavioral and autonomic expression of defensive reactions. Several results suggest that, along with GABA, glutamate and serotonin, nitric oxide (NO) may play a role in defense reactions mediated by this region. To further investigate this possibility we microinjected methylene blue (MB; 10, 30 or 100 nmol/0.5 µl) into the DPAG of rats submitted to the elevated plus-maze test, an animal model of anxiety. MB has been used as an inhibitor of soluble guanylate cyclase (sGC) to demonstrate cGMP-mediated processes, and there is evidence that NO may exert its biological effects by binding to the heme part of guanylate cyclase, causing an increase in cGMP levels. The results showed that MB (30 nmol) significantly increased the percent of time spent in the open arms (saline = 11.57 ± 1.54, MB = 18.5 ± 2.45, P<0.05) and tended to do the same with the percentage of open arm entries (saline = 25.8 ± 1.97, MB = 33.77 ± 3.07, P<0.10), but did not change the number of enclosed arm entries. The dose-response curve, however, had an inverted U shape. These results indicate that MB, within a limited dose range, has anxiolytic properties when microinjected into the DPAG.

Role of glutamate NMDA receptors and nitric oxide located within the periaqueductal gray on defensive behaviors in mice confronted by predator

“…In terms of the role of NO on defensive behaviors, many pharmacological studies have shown that systemic injections of NOS inhibitors (Volke et al 1995;Faria et al 1997;Volke et al 2003; for review, see Guimarães et al 2005) as well as intracerebral (e.g., dPAG, dorsal hippocampus, and medial amygdala) microinfusions of NOS inhibitors, guanylate cyclase inhibitors, or NO scavenger elicit anxiolytic-like effects in several animal models of anxiety such as the elevated plus-maze and light-dark compartment test De Oliveira and Guimarães 1999;Aguiar et al 2004; for review, see Guimarães et al 2005;Forestiero et al 2006;Spolidório et al 2007). …”

Protective Role of Methylene Blue in Alzheimer's Disease via Mitochondria and Cytochrome c Oxidase

“…Cytochrome c (cyt c) serves as electron carrier from ETC III to ETC IV. also used in the treatment of some psychiatric disorders because of its anxiolytic and antidepressant properties [138,139]. The typical dose of MB in clinical uses ranges between 1-2 mg/kg/day; however, MB can also be repeatedly administered at this dose up to 6 times over 24 h [135].…”

Behavioral, Physiological and Biochemical Hormetic Responses to the Autoxidizable Dye Methylene Blue

“…In another behavioral pharmacology study, three different MB doses (10, 30 or 100 nmol/0.5 μL) were injected intracranially into the dorsal periaqueductal grey of rats submitted to the elevated plus maze test [21]. The elevated plus maze test is widely used as a test of anxiety based on the natural aversion of rodents to heights and open spaces [22].…”