Decreased. A decrease in the HA level, especially related to the activation of H3R. Melanin-concentrating hormone (MCH) neurons express H3R through which HA directly inhibits release of MCH, an orexigenic peptide, with confirmed depressogenic effects. Moreover, other neural circuits may be influenced by lowered level of HA via H3R signaling, due to the crosstalk of HA-H3R signaling pathways with other depression-related neurotransmitters, such as 5-HT, DA, and GLU. Here, HRH3 is linked to major depressive disorder.