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

Abstract

The original version of this article unfortunately contained a mistake. The middle initial of the third author was not included. "Mark Millan" should be "Mark J. Millan."

Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties

“…Moreover, the compound is without effects when given at light onset. This chronobiotic profile of agomelatine is underlined by the lack of alterations in latencies to SWS and REM sleep and the preservation of the spectral components of the electroencephalogram (EEG) (Cajochen et al ., ; Quera Salva et al ., ; Descamps et al ., ). Indeed, melatonin and the melatonin agonist ramelteon exerted different effects on the parameters mentioned earlier and on power band spectra of the EEG, possibly reflecting the absence of antagonistic action at 5‐HT 2C receptors.…”

“…Actually, underscoring the importance of 5‐HT 2C receptor blockade for agomelatine, the 5‐HT 2C antagonist S 32006 (10 mg·kg −1 ), administered i.p. at the onset of the dark phase mimicked the increased SWS provoked by agomelatine, yet diminished REM sleep (Descamps et al ., ).…”

“…Agomelatine also influences the sleep/wake cycle architecture in control animals, as demonstrated by the enhanced duration of REM and slow wave sleep (SWS) for 3 h after acute oral administration of the drug (10 and 40 mg·kg −1 ) shortly before the dark phase of the L/D cycle in rats (Descamps et al ., ). The same modifications are observed during the following night without additional treatment with agomelatine.…”

Spike–Wave Discharges and Sleep–Wake States during Circadian Desynchronization: No Effects of Agomelatine upon Re-Entrainment

“…Although ineffective against epileptogenesis induced in the kainic acid-induced status epilepticus model, agomelatine given chronically prevents neuronal damage and comorbid depression in rats (Thekalarova et al, 2017 and2018). Melatonin and agomelatine may also alter sleep-wake architecture in the rat (Descamps et al, 2009). Considering the potential hypnotic and antiepileptic effect of agomelatine, our subchronic experiment was preceded by an acute study, which enabled us to disentangle the putative effects of agomelatine on sleep and epilepsy from the effects of the light phase delay on re-synchronization.…”

The melatonergic agonist and clinically active antidepressant, agomelatine, is a neutral antagonist at 5-HT2C receptors

“…Further, the melatonergic agonist properties of agomelatine favour sleep quality, onset and architecture, which are similarly perturbed in depression (Cajochen et al 2003 ;Germain & Kupfer, 2008 ;Millan, 2006). Blockade of SCN-localized 5-HT 2C Rs by agomelatine also participates in its promotion of restorative slowwave sleep and modulation of circadian rhythms (Descamps et al 2009 ;Kennaway & Moyer, 1998 ;Millan, 2005 ;Quera-Salva et al 2007).…”