In accordance with this, systemic administration of H3R (auto-receptor) antagonists ABT-288 or E177 can increase histamine release and improve fear memory retention in normal animals or rescue the deficits in chronic constrain stress model, MK-801 (an uncompetitive antagonist of NMDAR) induced amnesia or PTZ-induced memory deficits model [111, 112]. The gene discussed is HRH3; the disease is amnesia.