Implication of the ventrolateral part of the ventromedial hypothalamus in female sexual behavior

As many women experience problems with low sexual desire, further uncovering the neural pathway of female sexual behavior is necessary. Kisspeptin, a protein synthesized and secreted by two different neuronal populations in the hypothalamus, regulates ovulation and sexual maturation. New evidence indicates that it also plays an important role in sexual behavior. Recently, it has been shown in female mice that peripheral injection of kisspeptin (Kp-10) increases the expression of lordosis behavior and sexual preference towards the opposite sex. Although the neuronal pathways of kisspeptin in the control of female sexual behavior still need to be elucidated, a potential target for kisspeptin could be the neurons expressing the neuronal form of NOS (nNOS) in the ventrolateral part of the ventromedial hypothalamus (VMHvl). It was demonstrated that peripheral injection of kisspeptin in nNOS-KO mice had no effect on lordosis, whereas injection of SNAP (NO donor) in Kiss- KO mice induced lordosis at a level similar to the one expressed by WT mice, indicating that nNOS is a downstream target of kisspeptin. Also, neural tracing studies showed that nNOS neurons in the VMHvl receive kisspeptin projections, indicating its potential involvement in controlling sexual behavior as a relay nucleus.
To verify this hypothesis, C57bl/6 female mice were ovariectomized and implanted with an estradiol-containing implant. After a period of post-surgical recovery, the animals underwent stereotaxic surgery to implant a bilateral cannula aimed at the VMHvl. In different groups of animals, lordosis and sexual preference were evaluated after administration of the following drugs: Kp-10, L-NAME (nNOS inhibitor), SNAP/BAY (NO donor), and GnRH. The results revealed that Kp-10 and SNAP/BAY significantly increased lordosis, while L- NAME produced the opposite effect. However, all three substances had no effect on sexual preference. Interestingly, the administration of GnRH in the VMHvl had no effect on both lordosis and sexual preference.
These results demonstrate that the VMHvl is specifically involved in controlling lordosis behavior through kisspeptin and nNOS and not mate preferences, suggesting the existence of two separate neural circuits underlying lordosis behavior and sexual preference.