Involvement of the GABAergic system in the anxiolytic effect of sulfated polysaccharides from the red seaweed Gracilaria cornea

Sulfated polysaccharides (SP) are found in various marine organisms and their biological activities have aroused great interest in the medical sciences. This work presents the behavioral effects of SP isolated from the red marine alga Gracilaria cornea (total sulfated polysaccharides from G. cornea (TSP-Gc)) in animal models, such as the elevated plus maze (EPM), hole board, open field, and rotarod. The TSP-Gc was administered intraperitoneally to male mice at single doses of 0.1, 1, and 10 mg kg−1, while diazepam 1 or 2 mg kg−1 was used as a standard drug and flumazenil 2 mg kg−1 was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg kg−1), TSP-Gc 10 mg kg−1 significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field and rotarod. Flumazenil reversed not only the diazepam effect but also the TSP-Gc 10 mg kg−1 effect. In the same way, the dose of TSP-Gc 10 mg kg−1 increased the number of head dips in the hole-board test. An increased expression of α2-gamma-aminobutyric acid type A (α2-GABAA) receptor in the hippocampus (HC) was observed in the group treatment with diazepam (DZP) or TSP-Gc. However, the pretreatment with flumazenil (flumazenil (FLU) + DZP; FLU + TSP-Gc 10) reversed this effect. The results showed that sulfated polysaccharides from G. cornea (10 mg kg−1) presented an anxiolytic effect, disproving sedative effects, through GABAA receptor α2 subunit.