The present study was performed to investigate the effects of histamine H(1)-antagonists on the sleep-awake state in rats placed on a grid suspended over water in comparison with rats placed on sawdust. When rats were placed on the grid suspended over water, significant increases in the awake time and decreases in non-rapid eye movement (non-REM) sleep time were observed compared with in rats on sawdust, even when measured hourly for 6 h. Diphenhydramine, chlorpheniramine and promethazine caused a significant decrease in the awake time and increase in non-REM sleep time in rats placed on the grid suspended over water for 1-2 h and/or 2-3 h after administration. On the other hand, in rats placed on sawdust, no significant differences were observed in the awake time and non-REM sleep time with diphenhydramine and chlorpheniramine compared with the control. Different from these two drugs, promethazine caused a significant decrease in the awake time and increase in non-REM sleep time 1-2 h and 2-3 h after administration even when rats were placed on sawdust at a relatively high dose. These results clearly indicate that histamine H(1)-antagonists had potent effects on decreasing the awake time and increasing non-REM sleep time under the conditions of an activated histaminergic system.
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