EFFECTS OF THIOPERAMIDE, A HISTAMINE H-3 ANTAGONIST, ON THE STEP-THROUGH PASSIVE-AVOIDANCE RESPONSE AND HISTIDINE-DECARBOXYLASE ACTIVITY INSENESCENCE-ACCELERATED MICE

The effect of thioperamide, a histamine H-3 receptor antagonist, on le arning and memory was studied in the senescence-accelerated mice-prone strain (SAM-P/8) and normal-rate aging strain (SAM-R/1). In a passive avoidance test, SAM-P/8 mice of 12 months showed significant impairme nt of learning and memory compared with SAM-R/1 mice of the same age. Thioperamide significantly improved the response latency in SAM-P/8 mi ce when injected intraperitoneally at a dose of 15 mg/kg. The histidin e decarboxylase (HDC) activity in the forebrain was significantly lowe r in SAM-P/8 mice than in SAM-R/1 mice. Thioperamide administration si gnificantly potentiated HDC activity in the forebrain of SAM-P/8 mice as well as improving learning and memory. These results suggest that c entral histaminergic neurons may be involved in learning and memory im pairment of SAM-P/8 mice, although other possibilities are not ruled o ut.