Effects of histamine H₁ receptor antagonists on hippocampal theta rhythm during spatial memory performance in rats

The effects of histamine H₁ 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 H₁ receptor antagonists, decreased theta power at a dose of 35 mg/kg. These results suggest that anti-muscarinic receptor properties rather than anti-histamine H₁ receptor properties may affect hippocampal theta power during spatial memory deficit induced by promethazine, diphenhydramine and chlorphenilamine.