Ovariectomy Drives Asynchronous Changes in Serotonin Receptor 2A andTransporter Availability in Rats

Ovarian hormones have potent effects on key features of the serotonergic neurotransmission. This includes effects that may counterbalance each other, e.g. postsynaptic receptor changes and change in serotonin transporter (SERT) levels, which regulates synaptic serotonin. Such mechanisms may be implicated in the heightened risk for depressive episodes seen in perimenopause or postpartum. However, to what extent transition to hypogonadism in it-self drives such serotonin related risk mechanism remains elusive. Here we evaluate if ovarian hormone withdrawal affects postsynaptic serotonin receptor 2A (5-HT2A) and presynaptic SERT availability differently across the early withdrawal phase in ovariectomized (OVXed) relative to sham operated rats. Cortical (prefrontal cortex (PFC)) and subcortical (striatum) 5-HT2A receptor and SERT binding were quantified with autoradiography at 8 and 23 days after ovariectomy (OVX). We observed that 8 and 23 days after withdrawal the level of 5-HT2A receptor binding was decreased relative to sham, while SERT binding was unaltered, however, with a weak trend to decrease at day 23. The dataset available is small and the results should be viewed as preliminary. If replicated, these data highlight a potential phase-specific and predominantly early challenge of serotonergic neurotransmission when ovarian hormone levels decline abruptly, which may translate to the risk for psychopathology, e.g. depressive episodes postpartum or during menopausal transition in humans.