HRH3 and Alzheimer disease: In AD, H3R in the prefrontal cortex and hippocampus acts as a presynaptic auto-receptor coupled to Gαi/o-proteins that controls the synthesis and release of histamine, and as a heteroreceptor on histaminergic and non-histaminergic neurons in regulating the release of other neurotransmitters, including acetylcholine (ACh), dopamine, glutamate, norepinephrine, and gamma-aminobutyric acid (GABA) (Clapham and Kilpatrick, 1992; Ligneau et al., 1998; Bacciottini et al., 2002; Medhurst et al., 2007).