Differential effects of the 5-HT1A receptor agonist flesinoxan given locally or systemically on REM sleep in the rat.

The effects of flesinoxan, a selective 5-HT1A receptor agonist on spontaneous sleep, were studied in adult rats implanted for chronic sleep recordings. Flesinoxan was administered systemically or infused directly into the dorsal raphe nucleus, the left laterodorsal tegmental nucleus or the medial pontine reticular formation. Systemic administration of flesinoxan (0.03 and/or 0.06 micromol/kg) significantly increased wakefulness and sleep latencies, and reduced rapid eye movement (REM) sleep and the number of REM periods, during the first and/or second 2-h period after treatment. Direct infusion of the 5-HT1A receptor agonist (0.06 and/or 0.12 nmol) into the dorsal raphe nucleus induced a significant increment of REM sleep and augmented the number of REM periods during the second and/or third 2-h period of recording. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the laterodorsal tegmental nucleus reduced REM sleep and the number of REM periods, and augmented REM sleep latency during the first, second and/or third 2-h recording period. Finally, direct infusion of flesinoxan (0.48 nmol) into the medial pontine reticular formation decreased REM sleep and the number of REM periods, and increased REM sleep latency during the first and second 2 h of recording. Our results indicate that the 5-HT1A receptor is involved in the inhibitory effect of serotonin on brainstem structures that act to promote and to induce REM sleep.