Effects of the serotonin 5-HT2A/2C receptor agonist DOI and of the selective 5-HT2A or 5-HT2C receptor antagonists EMD 281014 and SB-243213, respectively, on sleep and waking in the rat

The effects of the serotonin 5-HT(2A/2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and of the selective 5-HT(2A) or 5-HT(2C) receptor antagonists 7-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl}-1H-indole-3-carbonitrile HCl (EMD 281014) and 5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline HCl (SB-243213), respectively, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Subcutaneous administration of DOI (0.35-0.7 mmol/kg) significantly increased waking and light sleep and reduced slow wave sleep, rapid-eye-movement (REM) sleep, and the number of REM periods. With subcutaneous EMD 281014 (1.2-4.8 mmol/kg) or SB-243213 (1.2-4.8 mmol/kg) a significant reduction in time spent in REM sleep was also seen. Pretreatment with EMD 281014 prevented the DOI-induced increase of waking and light sleep and the reduction of slow wave sleep. However, REM sleep remained suppressed. SB-243213 failed to reverse the changes of sleep and waking induced by DOI. Thus, on the basis of these results it appears that serotonin 5-HT(2A) receptor mechanisms might be responsible for the DOI-induced effects on waking and slow wave sleep.