5HT(1A)-receptor binding in the brain of cyclic and ovariectomized female rats

Although it has been reported that hypothalamic 5HT(1A)-receptor functionin g is modulated by oestrogen and that this modulation contributes to the reg ulation of female sexual behaviour, there have been no reports up to now sh owing changes in numbers of these receptors during the oestrus cycle and af ter oestrogen treatment. We therefore analysed 5HT(1A)-receptors in eight b rain areas of female rats at different stages of the oestrus cycle, and in ovariectomized (OVX) females without and with oestrogen replacement. In-vit ro receptor autoradiography with the agonist H-3-8-OH-DPAT(H-3-8-hydroxy-2- [di-n-propylamino]tetralin) was used to determine numbers and affinities of 5HT(1A)-receptors, To evaluate the hormonal state of the animals, serum co ncentrations of oestradiol, progesterone, luteinizing hormone (LH), and pro lactin were also measured, Hormone determinations confirmed the expected en docrine states of the animals. In the ventromedial hypothalamic nucleus, th e number of H-3-8-OH-DPAT binding sites (B-max-value) during oestrus was in creased compared to dioestrus yielding significant differences when using A NOVA statistics. In OVX females, the number of binding sites was decreased compared to pro-oestrus and oestrus, and after oestrogen replacement, it wa s as high as during oestrus. All other brain areas analysed (medial preopti c area, bed nucleus of the stria terminalis, lateral septum, cingulate cort ex, amygdala, hippocampal region CAI, and layers V and VI of the occipital cortex) showed no significant changes in 3H-8-OH-DPAT binding site numbers. Also the affinity of H-3-8-OH-DPAT binding sites did not change during the oestrus cycle, but in the medial preoptic area, oestradiol-treated OVX ani mals showed a tendency for increased affinity compared to untreated OVX fem ales, This was indicated by a change in K-d which appeared to be significan t when groups were compared with the t-test. We conclude from our data, tha t in the ventromedial hypothalamic nucleus, which is involved in the regula tion of sexual function, 5HT(1A)-receptors are up-regulated during oestrus, that ovariectomy reduces the receptor numbers, and that oestradiol replace ment counteracts the effect of ovariectomy. Since the ventromedial hypothal amic nucleus contains a high number of oestrogen receptive cells, our data indicate that oestrogen up-regulates 5HT(1A)-receptor expression in this nu cleus.