Additive effect of 5-HT2C and CB1 receptor blockade on the regulation of sleep–wake cycle

Bogáthy, Emese; Papp, Noémi; Tóthfalusi, László; Vas, Szilvia; Bagdy, György

doi:10.1186/s12868-019-0495-7

Cited by 11 publications

(3 citation statements)

References 49 publications

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“…In the present study, 1 mg/kg SB-242084 dose was chosen, based on former behavioral (Kennett et al, 1997;Martin et al, 2002;Opal et al, 2014) and sleep and/or EEG (Popa et al, 2005;Sorman et al, 2011;Bogathy et al, 2019) studies in rodents. Importantly, Kantor et al have demonstrated that although 0.3 and 1.0 mg/kg doses of the drug produced similar anxiolytic effects, only the higher dose affected the sleep-wake architecture prominently (wake-promoting effect with reduction of SWS-2), in Sprague-Dawley rats (Kantor et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Acute 5-HT2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram

et al. 2020

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Serotonin 2C receptors (5-HT 2C Rs) are implicated in the pathomechanism and treatment of anxiety and depression. Recently, as a new biomarker of depression, alterations in the gamma power of the electroencephalogram (EEG) have been suggested. Chronic treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant escitalopram has been shown to cause sleep-wake stage-dependent alterations in gamma power. However, despite the antidepressant potency of 5-HT 2C R-antagonists, there is no data available regarding the effects of selective 5-HT 2C R-antagonists on gamma activity. Therefore, we investigate the acute effect of the 5-HT 2C R-antagonist SB-242084 on gamma power in different vigilance stages when given in monotherapy, or in combination with chronic escitalopram treatment. We administered SB-242084 (1 mg/kg, intraperitoneally) or vehicle to EEG-equipped rats after a 21-day-long pretreatment with escitalopram (10 mg/kg/day, via osmotic minipumps) or vehicle. Frontoparietal EEG, electromyogram, and motor activity were recorded during the first 3 h of passive phase, after the administration of SB-242084. Quantitative EEG analysis revealed that acute SB-242084 increased gamma power (30-60 Hz) in light and deep slow-wave sleep, and passive wakefulness. However, in active wakefulness, rapid eye movement sleep, and intermediate stage, no change was observed in gamma power. The profile of the effect of SB-242084 on gamma power was similar to that produced by chronic escitalopram. Moreover, SB-242084 did not alter chronic escitalopram-induced effects on gamma. In conclusion, the similarity in the effect of the 5-HT 2C R-antagonist and chronic SSRI on gamma power provides further evidence for the therapeutic potential of 5-HT 2C Rantagonists in the treatment of depression and/or anxiety.

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Section: Discussionmentioning

confidence: 99%

Acute 5-HT2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram

et al. 2020

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“…Besides its opioid agonist and reuptake inhibitory effects, tramadol exerts inhibitory effects on several receptor types, such as muscarinic acetylcholine receptors, NMDA receptors, and 5-HT 2 receptors [ 2 ]. Importantly, the anticholinergic scopolamine, the NMDA antagonist ketamine, and the 5-HT 2C receptor antagonist SB-242084 all have fast-onset antidepressant properties [ 29 , 30 ], and also markedly suppress REM sleep [ 31 , 32 ], suggesting that the effect of tramadol on muscarinic, NMDA and 5-HT 2 receptors may be key in its antidepressant effect. Furthermore, data mining on the patient drug reviews database has also suggested that tramadol has a fast-onset antidepressant effect [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

EEG and Sleep Effects of Tramadol Suggest Potential Antidepressant Effects with Different Mechanisms of Action

et al. 2021

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Tramadol is a widely used, centrally acting, opioid analgesic compound, with additional inhibitory effects on the synaptic reuptake of serotonin and noradrenaline, as well as on the 5-HT2 and NMDA receptors. Preclinical and clinical evidence also suggests its therapeutic potential in the treatment of depression and anxiety. The effects of most widely used antidepressants on sleep and quantitative electroencephalogram (qEEG) are well characterized; however, such studies of tramadol are scarce. Our aim was to characterize the effects of tramadol on sleep architecture and qEEG in different sleep–wake stages. EEG-equipped Wistar rats were treated with tramadol (0, 5, 15 and 45 mg/kg) at the beginning of the passive phase, and EEG, electromyogram and motor activity were recorded. Tramadol dose-dependently reduced the time spent in rapid eye movement (REM) sleep and increased the REM onset latency. Lower doses of tramadol had wake-promoting effects in the first hours, while 45 mg/kg of tramadol promoted sleep first, but induced wakefulness thereafter. During non-REM sleep, tramadol (15 and 45 mg/kg) increased delta and decreased alpha power, while all doses increased gamma power. In conclusion, the sleep-related and qEEG effects of tramadol suggest antidepressant-like properties, including specific beneficial effects in selected patient groups, and raise the possibility of a faster acting antidepressant action.

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“…Chronic alcohol consumption compromises endocannabinoid signaling by decreasing CB1R expression in the brain and reducing its affinity for G-protein ( 21 ). Studies examining the role of the endocannabinoid system in sleep have found that CB1 agonists promote sleep and administration of CB1 antagonists increases time spent in active wakefulness in animal models ( 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

FAAH and CNR1 Polymorphisms in the Endocannabinoid System and Alcohol-Related Sleep Quality

et al. 2021

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Sleep disturbances are common among individuals with alcohol use disorder (AUD) and may not resolve completely with short-term abstinence from alcohol, potentially contributing to relapse to drinking. The endocannabinoid system (ECS) is associated with both sleep and alcohol consumption, and genetic variation in the ECS may underlie sleep-related phenotypes among individuals with AUD. In this study, we explored the influence of genetic variants in the ECS (Cannabinoid receptor 1/CNR1: rs806368, rs1049353, rs6454674, rs2180619, and Fatty Acid Amide Hydrolase/FAAH rs324420) on sleep quality in individuals with AUD (N = 497) and controls without AUD (N = 389). We assessed subjective sleep quality (from the Pittsburgh Sleep Quality Index/PSQI) for both groups at baseline and objective sleep efficiency and duration (using actigraphy) in a subset of individuals with AUD at baseline and after 4 weeks of inpatient treatment. We observed a dose-dependent relationship between alcohol consumption and sleep quality in both AUD and control groups. Sleep disturbance, a subscale measure in PSQI, differed significantly among CNR1 rs6454674 genotypes in both AUD (p = 0.015) and controls (p = 0.016). Only among controls, neuroticism personality scores mediated the relationship between genotype and sleep disturbance. Objective sleep measures (sleep efficiency, wake bouts and wake after sleep onset), differed significantly by CNR1 rs806368 genotype, both at baseline (p = 0.023, 0.029, 0.015, respectively) and at follow-up (p = 0.004, p = 0.006, p = 0.007, respectively), and by FAAH genotype for actigraphy recorded sleep duration at follow-up (p = 0.018). These relationships suggest a significant role of the ECS in alcohol-related sleep phenotypes.

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Additive effect of 5-HT2C and CB1 receptor blockade on the regulation of sleep–wake cycle

Cited by 11 publications

References 49 publications

Acute 5-HT2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram

Acute 5-HT2C Receptor Antagonist SB-242084 Treatment Affects EEG Gamma Band Activity Similarly to Chronic Escitalopram

EEG and Sleep Effects of Tramadol Suggest Potential Antidepressant Effects with Different Mechanisms of Action

FAAH and CNR1 Polymorphisms in the Endocannabinoid System and Alcohol-Related Sleep Quality

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