A study of the brain structures involved in the acute effects of fluoxetine on REM sleep in the rat

Abstract

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.

Fluoxetine: a case history of its discovery and preclinical development

“…Interestingly, similar findings were obtained in preclinical research, where both acute [77] and chronic administrations of fluoxetine were effective in decreasing REM sleep in rodents [78].…”

Association of Serotonin Transporter Gene Polymorphism with Obstructive Sleep Apnea Syndrome

“…Systemic infusion of selective serotonin reuptake inhibitors significantly reduces REM sleep (REMS) and the number of REM periods. Direct infusion into dorsal raphe nucleus increases REMS and the number of REM periods and decreases REMS latency 13 …”

“…Direct infusion into dorsal raphe nucleus increases REMS and the number of REM periods and decreases REMS latency. 13 It is apparent that serotonin (5-HT or 5-hydroxytryptamine), a neurotransmitter in the central nervous system, is involved in the regulation of a variety of visceral functions and physiologic functions such as sleep. The synaptic 5-HT is inactivated by presynaptic reuptake, which is mediated by the serotonin transporter.…”

Nitric oxide production in the basal forebrain is required for recovery sleep

“…NO concentrations undergo state-dependent modulation during the sleep-wake cycle both in the thalamus and the cortex (Burlet and Cespuglio 1997;Williams et al 1997), but there are no measurements of NO concentrations during prolonged wakefulness in any brain area. Several previous studies have shown that intraperitoneal, subcutaneous or intracerebroventricular administration of inhibitors of the NO-synthesizing enzyme NO synthase (NOS) decreases spontaneous sleep (Kapas et al 1994;Dzoljic et al 1996;Monti et al 1999Monti et al , 2001Ribeiro et al 2000;Monti and Jantos 2005;Ribeiro and Kapas 2005;Cavas and Navarro 2006) whereas NO donors increase it Monti and Jantos 2004a), suggesting that NO may have a role as a sleepfacilitating agent. Local injections of NOS inhibitors into the pons, including the cholinergic laterodorsal/pedunculopontine tegmental nuclei (LDT/PPT) as well as the dorsal raphe nucleus, have generally also decreased either REM sleep or both NREM and REM sleep (Datta et al 1997;Leonard and Lydic 1997;Hars 1999;Monti et al 1999Monti et al , 2001.…”