The fact that thioperamide treatment 1) prevents cognitive and motor learning deficits, 2) ameliorates striatal neuropathology, 3) ameliorates morphological alterations and 4) prevents the loss of D1R-H3R heteromers at 6 mo and 8 mo of age in a mouse model of HD is suggestive that thioperamide, or a future pharmacologically improved H3R antagonist specifically targeting D1R-H3R heteromers, can be used to treat HD symptoms. Here, HRH3 is linked to Huntington disease.