Effects of two selective 5-HT2C receptor-acting compounds into the ventral hippocampus of rats exposed to the elevated plus-maze

This study investigated the effects of two selective serotonin2C (5-hydroxytryptamine, 5-HT2C) receptor-acting compounds into the ventral hippocampus (VH) of rats exposed to the elevated plus-maze (EPM). In the first experiment, rats were exposed to the EPM 10 min following VH infusions of either vehicle or the selective 5-HT2C-receptor agonist RO-60-0175 (0.3, 1.0, 3.0 and 10.0μg). In addition to conventional parameters of open arm exploration (i.e. percentages of open arm entries and of time spent in these arms), risk assessmentrelated behaviors were recorded as anxiety-like measures in EPM scoring. RO-60-0175 selectively decreased open arm exploration at the dose of 1.0 μg, while inducing locomotor-suppressant effects at the two highest doses. In the second experiment, VH infusions of the selective 5-HT2C antagonist RS 102221 (0.75, 1.25 and 2.5 μg) did not affect open arm exploration, while reducing risk assessment in the closed ones. This behavioral profile of risk assessment is suggestive of an anxiolytic-like action. These results further corroborate our previous findings showing that VH 5-HT2C receptor activation elicits anxiogenic-like and locomotor-suppressant effects, and suggest that the selective blockade of this receptor is accompanied by an anxiolytic-like action as detected by ethologically derived measures in the EPM.