5HT1A‐Receptor Binding in the Brain of Cyclic and Ovariectomized Female Rats

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Abstract
Although it has been reported that hypothalamic 5HT1A-receptor functioning is modulated by oestrogen and that this modulation contributes to the regulation of female sexual behaviour, there have been no reports up to now showing changes in numbers of these receptors during the oestrus cycle and after oestrogen treatment. We therefore analysed 5HT1A-receptors in eight brain areas of female rats at different stages of the oestrus cycle, and in ovariectomized (OVX) females without and with oestrogen replacement. In-vitro receptor autoradiography with the agonist 3H-8-OH-DPAT(3H-8-hydroxy-2-[di-n-propylamino]tetralin) was used to determine numbers and affinities of 5HT1A-receptors. To evaluate the hormonal state of the animals, serum concentrations of oestradiol, progesterone, luteinizing hormone (LH), and prolactin were also measured. Hormone determinations confirmed the expected endocrine states of the animals. In the ventromedial hypothalamic nucleus, the number of 3H-8-OH-DPAT binding sites (Bmax-value) during oestrus was increased compared to dioestrus yielding significant differences when using ANOVA statistics. In OVX females, the number of binding sites was decreased compared to pro-oestrus and oestrus, and after oestrogen replacement, it was as high as during oestrus. All other brain areas analysed (medial preoptic area, bed nucleus of the stria terminalis, lateral septum, cingulate cortex, amygdala, hippocampal region CA1, 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 3H-8-OH-DPAT binding sites did not change during the oestrus cycle, but in the medial preoptic area, oestradiol-treated OVX animals showed a tendency for increased affinity compared to untreated OVX females. This was indicated by a change in Kd which appeared to be significant when groups were compared with the t-test. We conclude from our data, that in the ventromedial hypothalamic nucleus, which is involved in the regulation of sexual function, 5HT1A-receptors are up-regulated during oestrus, that ovariectomy reduces the receptor numbers, and that oestradiol replacement counteracts the effect of ovariectomy. Since the ventromedial hypothalamic nucleus contains a high number of oestrogen receptive cells, our data indicate that oestrogen up-regulates 5HT1A-receptor expression in this nucleus.