Anxiolytic-like effects of DOI microinjections into the hippocampus (but not the amygdala nor the PAG) in the mice four plates test

Anxiolytic-like effects of DOI, a 5-HT2A/2C agonist have been observed in the four plates test (FPT) after intra-peritoneal administrations. In the present study, DOI (1 μg, 2 μg or 5 μg per mice) was directly injected to three brain structures, the hippocampus, the amygdala and the periaqueductal gray matter (PAG). Tests were carried out immediately after injections. In amygdala and PAG, DOI exerted an anxiogenic-like effect. In the hippocampus, a strong anxiolytic-like effect was found only when injecting 5 μg DOI/mice in the FPT, with a size effect comparable to the anxiolytic-like effect of diazepam 1 mg/kg injected intra-peritoneally. DOI or vehicle injections did not affect locomotor activity. These results help us to understand mechanisms of action of DOI in animal models of anxiety, probably through an interaction with other neurotransmitter system, which may take place in the hippocampus.