Resumo

Guanosine and other extracellular guanine-based purines (GBPs), namely GTP, GDP and GMP, have been shown to exert effects on the Central Nervous System (CNS) not directly related to the modulation of G-proteins. Guanosine has been shown to produce neuroprotective effects to excitotoxic conditions, hypoxia and ischemia; guanosine also presents amnesic, anxiolytic and antinociceptive effects, an anticonvulsant action against seizures induced by glutamatergic agents, and partial reversion of hyperlocomotion induced by N-Methyl-D-aspartate antagonists. Although the effects of guanosine have been widely studied in vivo and in vitro against several types of injury, little is known about its electrophysiological effects in CNS and its actions in a system in homeostasis. The aim of this study was to investigate behavioral and electrophysiological effects of intraperitoneal (i.p.) administration of guanosine. For this purpose, we recorded and analyzed epidural electroencephalogram (EEG) of male adult Swiss albino mice (3-4 months of age, 30-50g). For EEG registering, two stainless steel electrodes, 0.5 mm diameter, were placed bilaterally over the associative motor cortex (AP -2.0 mm, LR ± 1.2 mm) at the dura-mater, and a reference screw was placed occipitally. Mice were divided into six groups according to treatment: NaCl 0.9% (n = 7), guanosine 15 mg/kg (n=4), 30 mg/kg (n=5), 60 mg/kg (n=6) and 120 mg/kg (n=11), and diazepam (5 mg/kg, 1 mL/kg, n=5). All solutions were administered i.p. and all saline and guanosine solutions were administered in a volume corresponding to 10 ml/kg and warmed up to 37.5 ˚C. The signal acquisition and behavioral observation were made from 10 minutes before until 90 minutes after the administration of one of the six treatments. Immediately after the intraperitoneal injection, mice were transferred from an observation box where they were previously habituated to an Open-Field apparatus which include video recording and analysis of the traveled distance. Our findings point to a dose-dependent reduction in locomotion promoted by guanosine administration. In relation to control group mean, the groups receiving 15, 30, 60 and 120 mg/kg of guanosine traveled 70.5 ± 9.1%, 44.3 ±6.2%, 35.1 ± 8.5% and 64.7 ± 7.1% (mean ± standard error mean), respectively. The group receiving diazepam 5 mg/kg traveled 23.9 ± 9.3 % in relation to control mean. Time-frequency decomposition of EEG signal detected the presence of more prominent slow waves (delta band, 0.1-5 Hz) during resting immobility, and a less prominent upper theta rhythm (6-8 Hz) in mice receiving guanosine compared to controls. A similar increase of delta activity was seen in mice receiving diazepam 5 mg/kg, but in this case theta oscillations seemed completely abolished. Guanosine reduced the total distance traveled during the 90 minutes of observation up to the 60 ml/kg dosage and lost effect at the dosage of 120 mg/kg. This reduction was associated with an emerging activity of delta oscillations, as also induced by diazepam. In contrast to diazepam, however, guanosine did not impair responsiveness to exterior stimuli, what may be correlated with the fact of preserved activity of theta oscillations and hippocampus functionality.