Rapid effects of the G-protein coupled oestrogen receptor (GPER) on learning and dorsal hippocampus dendritic spines in female mice

Recently, oestrogen receptors (ERs) have been implicated in rapid learning processes. We have previously shown that 17β-estradiol, ERα and ERβ agonists can improve learning within 40 min of drug administration in mice. However, oestrogen action at the classical receptors may only in part explain these rapid learning effects. Chronic treatment of a G-protein coupled oestrogen receptor (GPER) agonist has been shown to affect learning and memory in ovariectomized rats, yet little is known about its rapid learning effects. Therefore we investigated whether the GPER agonist G-1 at 1 μg/kg, 6 μg/kg, 10 μg/kg, and 30 μg/kg could affect social recognition, object recognition, and object placement learning in ovariectomized CD1 mice within 40 min of drug administration. We also examined rapid effects of G-1 on CA1 hippocampal dendritic spine density and length within 40 min of drug administration, but in the absence of any learning tests. Results suggest a rapid enhancing effect of GPER activation on social recognition, object recognition and object placement learning. G-1 treatment also resulted in increased dendritic spine density in the stratum radiatum of the CA1 hippocampus. Hence GPER, along with the classical ERs, may mediate the rapid effects of oestrogen on learning and neuronal plasticity. To our knowledge, this is the first report of GPER effects occurring within a 40 min time frame.