Role of N-Arachidonoyl-Serotonin (AA-5-HT) in Sleep-Wake Cycle Architecture, Sleep Homeostasis, and Neurotransmitters Regulation

Abstract

The endocannabinoid system comprises several molecular entities such as endogenous ligands [anandamide (AEA) and 2-arachidonoylglycerol (2-AG)], receptors (CB1 and CB2), enzymes such as [fatty acid amide hydrolase (FAHH) and monoacylglycerol lipase (MAGL)], as well as the anandamide membrane transporter. Although the role of this complex neurobiological system in the sleep–wake cycle modulation has been studied, the contribution of the blocker of FAAH/transient receptor potential cation channel subfamily V member 1 (TRPV1), N-arachidonoyl-serotonin (AA-5-HT) in sleep has not been investigated. Thus, in the present study, varying doses of AA-5-HT (5, 10, or 20 mg/Kg, i.p.) injected at the beginning of the lights-on period of rats, caused no statistical changes in sleep patterns. However, similar pharmacological treatment given to animals at the beginning of the dark period decreased wakefulness (W) and increased slow wave sleep (SWS) as well as rapid eye movement sleep (REMS). Power spectra analysis of states of vigilance showed that injection of AA-5-HT during the lights-off period diminished alpha spectrum across alertness in a dose-dependent fashion. In opposition, delta power spectra was enhanced as well as theta spectrum, during SWS and REMS, respectively. Moreover, the highest dose of AA-5-HT decreased wake-related contents of neurotransmitters such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT) whereas the levels of adenosine (AD) were enhanced. In addition, the sleep-inducing properties of AA-5-HT were confirmed since this compound blocked the increase in W caused by stimulants such as cannabidiol (CBD) or modafinil (MOD) during the lights-on period. Additionally, administration of AA-5-HT also prevented the enhancement in contents of DA, NE, EP, 5-HT and AD after CBD of MOD injection. Lastly, the role of AA-5-HT in sleep homeostasis was tested in animals that received either CBD or MOD after total sleep deprivation (TSD). The injection of CBD or MOD increased alertness during sleep rebound period after TSD. However, AA-5-HT blocked this effect by allowing animals to display an enhancement in sleep across sleep rebound period. Overall, our findings provide evidence that AA-5-HT is an important modulator of sleep, sleep homeostasis and neurotransmitter contents.

Sleep and Neurochemical Modulation by DZNep and GSK-J1: Potential Link With Histone Methylation Status

“…In addition, rats were connected to a 6-channel slip-ring commutator through a 50 cm cable (Plastics One, Roanoke, VA, United States), which allowed free moving of animal around the cage. The EEG/EMG electrodes surgical procedure as well as habituation conditions were carried out as reported previously ( Murillo-Rodríguez et al, 2017 ).…”

“…The sleep data were collected during the following 4 h post-injections sampled in periods of 12 s (epochs). Next, differentiation of wakefulness (W), slow wave sleep (SWS), or rapid eye movement sleep (REMS) was based on the characterization of each phase by the aid of the sleep-scoring program (ICELUS) as previously reported ( Murillo-Rodríguez et al, 2017 ). One observer blind to the experiments analyzed sleep recordings.…”

“…This data provided information about quality rather than quantity of the sleep stages under the influence of treatments. Data were analyzed as previously reported ( Murillo-Rodríguez et al, 2017 ). One observer blind to the experiments analyzed power spectra.…”

“…Previous results have shown the role of the nucleus accumbens (AcbC) in the sleep-wake cycle modulation ( Qiu et al, 2012 ). Moreover, studies from our group have demonstrated reliable measurements of sleep-related neurochemicals such as dopamine (DA), norepinephrine (NE), epinephrine (EP), serotonin (5-HT), of samples collected from AcbC ( Mijangos-Moreno et al, 2014 , 2016 ; Murillo-Rodríguez et al, 2017 ). Thus, we determined whether DZNep or GSK-J1 might exert changes in the levels of these neurochemicals as characterized from microdialysis samples collected from AcbC.…”

Schisandrin B exerts hypnotic effects in PCPA‑treated rats by increasing hypothalamic 5‑HT and γ‑aminobutyric acid levels

“…According to a previous study in rats, SchB exerts sedative and hypnotic effects, which are associated with the upregulation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) and both the mRNA and protein expression of its two receptors, GABA A receptor α1 (GABA A Rα1) and GABA A receptor γ2 (GABA A Rγ2) (6). However, reports have demonstrated that as well as GABA, 5-hydroxytryptamine (5-HT), another central neurotransmitter, also plays an important role in sleep regulation (7,8). The decarboxylation of 5-hydroxytryptophan, a 5-HT precursor, is a key step during the synthesis of 5-HT, and the tryptophan hydrogenase enzyme is essential for this step (9).…”