with increased HA resulting in decreased DA signaling and vice versa (62, 63). H2 and H3 receptors are enriched in the striatum and cortex, regions of the brain implicated in TS (64), and studies of rodents with decreased brain HA show increased sensitivity to stereotypies when administered DA agonists (65). As H3R antagonists and inverse agonists are in late-stage clinical development and being considered for other neuropsychiatric indications (66, 67), there may well be near-term opportunities to translate a deeper understanding of the relationship of HA and tics into novel treatment approaches.
