sb-243213 and 4-iodo-2-5-dimethoxyphenylisopropylamine

The effects of the 5-HT(2A/2C) receptor agonist DOI and of the selective 5-HT(2A) or 5-HT(2C) receptor antagonists EMD 281014 and SB-243213, respectively, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. The serotonergic ligands were microinjected directly into the dorsal raphe nucleus (DRN). Infusion of DOI (1.4-5.6 mmol) into the DRN induced a significant reduction of REM sleep (REMS) and of the number of REM periods. Following the microinjection of EMD 281014 (5.6 mmol) or SB-243213 (1.4-2.8 mmol) light sleep (LS) was slightly but significantly augmented. Pretreatment with EMD 281014 or SB-243213 antagonized the DOI-induced decrease of REMS. It is proposed that suppression of REMS after DOI microinjection into the DRN is related to the activation of GABAergic projection neurons that synapse cholinergic neurons in the laterodorsal and peduncunculopontine tegmental nuclei (LDT/PPT) involved in the promotion of REMS.

Topics: Amphetamines; Animals; Dose-Response Relationship, Drug; Drug Interactions; Electroencephalography; Electromyography; Indoles; Male; Piperazines; Pyridines; Raphe Nuclei; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Serotonin 5-HT2 Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Sleep; Wakefulness

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.

Topics: Amphetamines; Animals; Indoles; Injections, Subcutaneous; Male; Piperazines; Pyridines; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Serotonin Antagonists; Serotonin Receptor Agonists; Sleep; Sleep, REM; Wakefulness