Effects of the 5-HT1A receptor ligands flesinoxan and WAY 100635 given systemically or microinjected into the laterodorsal tegmental nucleus on REM sleep in the rat.
The effects of flesinoxan, a selective 5-HT1A receptor agonist, and of WAY 100635, a selective high affinity 5-HT1A receptor antagonist, on spontaneous sleep were studied in adult rats implanted for chronic sleep recordings. Systemic administration of flesinoxan (0.03 and/or 0.06 micromol/kg, s.c.) increased waking (W) and sleep latencies and reduced REM sleep (REMS) and the number of REM periods during the first and/or second 2-h period after treatment. Systemic injection of WAY 100635 (0.46 and/or 0.92 micromol/kg, s.c.) augmented W and REMS latency and reduced REMS and the number of REM periods during the 6-h recording period. Microinjection of flesinoxan (0.03, 0.06 and/or 0.12 nmol) into the laterodorsal tegmental nucleus (LDT) reduced REMS and the number of REM periods, and augmented REMS latency during the first, second, and/or third 2-h recording period. Direct infusion of WAY 100635 (0.06 and/or 0.12 nmol) into the LDT increased REMS and the number of REM periods during the first and/or second 2 h of recording. It is proposed that the activation by flesinoxan of postsynaptic 5-HT1A receptors located in the LDT could be responsible for the REMS suppression. The increase in REMS after the blockade of postsynaptic 5-HT1A receptors in the LDT by WAY 100635 further supports our proposal. The effects of systemic flesinoxan on sleep variables may depend mainly on the activation of postsynaptic 5-HT1A receptors, whereas the effects corresponding to systemic WAY 100635 may be predominantly related to the blockade of presynaptic somatodendritic 5-HT1A autoreceptors.
Monti
Jaime M
JM
Department of Pharmacology and Therapeutics, Clinics Hospital, M.D. 2833/602 Zudañez Street, Montevideo 11300, Uruguay. jmonti@mednet.org.uy
Jantos
Héctor
H
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D008297:Male; D008845:Microinjections; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012895:Sleep, REM / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects
D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C056895:flesinoxan; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide