R-citalopram Attenuates Anxiolytic Effects of Escitalopram in a Rat Ultrasonic Vocalisation Model

Escitalopram mediates the serotonin reuptake inhibitory effect of citalopram. To investigate the potential interactive effects between escitalopram and R-citalopram, they were studied at standard and elevated serotonin levels in a model predictive of anxiolytic activity (inhibition of footshock-induced ultrasonic vocalisation in adult rats). At standard levels, citalopram partially inhibited (64%) and escitalopram abolished (97%) vocalisation. Co-treatment with L-5-hydroxytryptophan resulted in complete inhibition with citalopram and a substantially enhanced response to escitalopram, while R-citalopram increased the vocalisation significantly. Furthermore, R-citalopram attenuated the effect of escitalopram. These findings may be relevant to the enhanced clinical efficacy seen with escitalopram compared to citalopram.