Acute administration of the novel serotonin and noradrenaline reuptake inhibitor, S33005, markedly modifies sleep–wake cycle architecture in the rat

Abstract

These results demonstrate a pattern of influence of S33005 upon sleep-wake architecture in rats which is globally consistent with antidepressant properties, but with a distinctive enhancement of restorative slow-wave sleep.

S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models

“…Inasmuch as activation of 5-HT 2B receptors in the amygdala enhances social interaction, their blockade is unlikely to participate in the anxiolytic properties of S32006 (Kennett et al 1996a;Millan 2003). Nonetheless, 5-HT 2B receptors modulate sleep-wake cycle architecture (Smith et al 2002;Kantor et al 2004Kantor et al , 2005Cespuglio et al 2005;Millan 2006), so a possible role of their blockade in the influence of S32006 upon sleep (Descamps-Lefebvre et al 2008) should not be discounted.…”

Influence of the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist, agomelatine, on the rat sleep–wake cycle architecture

“…Possible clinical pertinence of findings: mood and cognition As pointed out in the "Introduction" section, many classes of antidepressant, including tricyclics, SSRIs, SNRIs, and MAO inhibitors, reduce REM sleep in patients (however, insomnia and the disruption of sleep architecture is observed only in 40-60% of outpatients with a diagnosis of major depression) and in rats but it remains controversial whether there is any causal relationship between this effect and improved mood (Winokur et al 2001;Rijnbeek et al 2003;Cespuglio et al 2005;Millan 2006). Indeed, despite experimental and clinical evidence for antidepressant properties of agomelatine, it did not reduce REM sleep, mimicking the lack of REM suppression seen with mirtazapine (which shares the 5-HT 2C antagonist but not melatoninergic properties of agomelatine; Millan et al 2000;Schittecatte et al 2002).…”

“…Interestingly, total sleep deprivation or selective reduction of REM sleep rapidly improves depressed mood (Wirz-Justice and Van den Hoofdakker 1999;Millan 2006). In keeping with these observations, diverse classes of antidepressant suppress REM sleep in both depressed patients and in healthy volunteers, as well as in rodents (Cespuglio et al 2005), while a rebound elevation in REM sleep has been documented upon withdrawal of SSRIs and SNRIs in patients (Trivedi et al 1999;Cespuglio et al 2005). In contrast to the above-mentioned drugs, the atypical agent mirtazapine does not suppress REM sleep despite clinically relevant antidepressant properties (Schittecatte et al 2002) In a polysomnographic study conducted in depressed patients, it appears that agomelatine improves sleep continuity.…”

“…The procedure employed was essentially that described previously (Clement et al 2003;Cespuglio et al 2005). Polygraphic recordings (Embla set-up, Medcare, Iceland) were initiated and continued until stable baselines of sleep-wake states were obtained two full 24 h cycles; each cycle 12 h dark-12 h light.…”

“…For hourly comparisons, the second factor was concatenated with time. Finally, the cosine fit analysis was applied as described previously for the circadian rhythm analysis (Cespuglio et al 2005). In this respect, averaged data were treated in 1-h periods, and the validity of fitting assessed by a Fisher's F-test.…”