A study of the brain structures involved in the acute effects of fluoxetine on REM sleep in the rat.
The effects of acute administration of fluoxetine, a selective serotonin reuptake inhibitor on spontaneous sleep, were studied in adult rats implanted for chronic sleep recordings. Fluoxetine was administered systemically or infused directly into the dorsal raphe nucleus (DRN), the right laterodorsal tegmental nucleus (LDT) or the medial pontine reticular formation (mPRF). Systemic administration of fluoxetine (3.0-12.0 micromol/kg) significantly reduced rapid-eye-movement sleep (REMS) and the number of REM periods; REMS latency was augmented. Direct infusion of fluoxetine (1.0 nmol) into the DRN induced a significant increment of REMS and of the number of REM periods whereas REMS latency was reduced. Microinjection of fluoxetine into the LDT (1.0 nmol) or the mPRF (0.8 nmol) decreased REMS and the number of REM periods whereas REMS latency was augmented. Pre-treatment with the selective 5-HT1A receptor antagonist WAY 100635 prevented the reduction of REMS induced by the microinjection of fluoxetine into the LDT. Our results indicate that the fluoxetine-induced suppression of REMS is related to the inhibition of brainstem structures involved in the promotion and the induction of REMS. The decrease of REMS would be dependent upon the activation of several 5-HT receptor subtypes, including the 5-HT1A receptor.
Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay. jmonti@mednet.org.uy
Jaime M
JM
Monti
Héctor
H
Jantos
D000818:Animals; D001931:Brain Mapping; D001933:Brain Stem / Q000187:drug effects*; D004292:Dominance, Cerebral / Q000187:drug effects; D004333:Drug Administration Routes; D004569:Electroencephalography / Q000187:drug effects; D004576:Electromyography / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D012154:Reticular Formation / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D012890:Sleep; D012895:Sleep, REM / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects
D005473:Fluoxetine; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide