Long lasting behavioral and electrophysiological action of early administration of guanosine: Analysis in the adult rat brain

Guanosine (GUO) is a guanine-based purine that has been extensively described in the literature as an endogenous nucleoside with participation in brain cell signalling pathways. Here, we evaluated whether chronic treatment with exogenous guanosine during brain development altered behavioral and electrophysiological parameters in adulthood. Rat pups received a daily intraperitoneal injection of 10, 50 or 100 mg/ kg/day GUO, or saline solution or no treatment (naive group) from postnatal (P) day 7 to P27. At P 60-65 the animals were behaviorally tested in the Elevated Plus-Maze (EPM). On P90-100, the electrophysiological phenomenon known as cortical spreading depression (CSD) was recorded on the right cortical surface for 4 h. With the EPM task, GUO treatment was associated with a significant increase in rearing behavior and a non-significant trend towards anxiogenic behavior. In a dose-dependent manner, GUO significantly (p < 0.01) increased weight gain on P90, and reduced the CSD propagation velocity from 3.42 +/- 0.10 and 3.43 +/- 0.10 mm/min in the Naive and Vehicle controls, respectively, to 3.05 +/- 0.12 mm/min, 2.87 +/- 0.07 mm/min and 2.25 +/- 0.25 mm/min in the groups treated with 10, 50 and 100 mg/kg/d GUO, respectively. The results confirmed the hypothesis that the chronic treatment with GUO early in life modulates CSD and body weight. Data on CSD propagation suggest that, besides its suppressing action on glutamatergic transmission (via enhancement of astrocytic glutamate uptake), GUO might act as an antioxidant in the brain, a hypothesis that deserves further exploration.