Effects of histamine H(1) receptor antagonists on hippocampal theta rhythm during spatial memory performance in rats

The effects of histamine H(1) receptor antagonists (promethazine, diphenhydramine, chlorphenilamine and triprolidine) on hippocampal theta rhythm during eight-arm radial maze performance were investigated using rats. Promethazine showed a significant increase in the number of total errors and working memory errors at doses of 10 and 20 mg/kg, and a significant increase was also observed in reference memory errors at a dose of 20 mg/kg. Diphenhydramine and chlorphenilamine at a dose of 20 mg/kg and triprolidine at a dose of 35 mg/kg also caused significant increases in the number of total, reference memory and working memory errors. Promethazine, diphenhydramine and chlorphenilamine, having potent anti-muscarinic receptor properties, increased hippocampal theta power during radial maze performance at a dose of 20 mg/kg. On the other hand, triprolidine, which has weak anti-muscarinic receptor properties compared with other histamine H(1) receptor antagonists, decreased theta power at a dose of 35 mg/kg. These results suggest that anti-muscarinic receptor properties rather than anti-histamine H(1) receptor properties may affect hippocampal theta power during spatial memory deficit induced by promethazine, diphenhydramine and chlorphenilamine.