Resumo

Introduction: The modulation of glutamatergic system has received considerable attention over the last years as potential target to develop anxiolytic drugs. Over the past 10 years, our group has shown that guanine-based purines (GBPs), exhibit important neuromodulatory function, including the extracellular antagonism of glutamatergic system. Objective: Considering the effects of GBPs on glutamatergic system and the involvement of glutamate in the pathophysiology of anxiety, this work aimed to investigate the GBPs` effects (by guanosina 5`monophosphate (GMP) administration in rodents) on classical anxiety-related behavioral tasks. Methods: Adult male Wistar rats were (i.p.) pretreated with GMP (10, 25, 50, 100 and 150 mg/kg); or saline (NaCl 0.9%) (control); or, diazepam (2 mg/kg), (positive control). One hour after the injection, the anxiety-related behaviors for each animal was evaluated in the light/dark, elevated plus-maze, and open field tasks. Additionally, purines concentration in the cerebrospinal fluid (CSF) was verified. All experimental procedures were performed in accordance with Brazilian Society for Neuroscience and Behavior’s recommendations for animal care. Results: The administration of GMP 50 mg/kg induced anxiolytic-like behavior, similar to diazepam, in the light/dark and the elevated plus maze tasks, but did not altered the open field performance and the CSF purine profile. In the light/dark task, the animals treated with diazepam or GMP (25 and 50 mg/kg) exhibited a significant increase in the total exploration time on the light compartment (n = 10 per group, P < 0.05) and, only GMP 50 mg/kg increases the number of transitions between the light and dark compartments compared to saline (n = 10 per group, P < 0.05). In the elevated plus-maze, GMP (25 and 50 mg/kg) and diazepam presented a significant increase in the time spent in open arms, compared with the saline group (n = 10 per group, P < 0.05). No changes in the locomotor activity nor the time spent in inner area of the open field arena (n=7-9) or CSF purines concentration (n=7-9) were found for either GMP or diazepam treated animals, when compared with saline group. Conclusion: The main finding of the present work was that GMP at the dose of 50 mg/kg was able to consistently reproduce the anxiolytic effects of diazepam in anxiety-related behaviors. Thus, this study suggests that acute administration of GMP was able to decrease the levels of anxiety in classical behavioral tasks. Nevertheless, more studies, especially on pharmacokinetics, are needed to better understand the exactly mechanism by which GMP exert the anxiolytic effects.