Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption

Sharma, Rishi; Sahota, Pradeep; Thakkar, Mahesh

doi:10.1111/jnc.14054

Cited by 16 publications

(6 citation statements)

References 45 publications

(135 reference statements)

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“…For instance, in adult rodents, acute binge alcohol has been shown to have sleep disrupting effects (Sharma, Sahota, & Thakkar, 2014), associated with reductions in the expression of equilibrative nucleoside transporter 1 (ENT1) (Sharma, Gonda, & Tarazi, 2018). Chronic ethanol administration has also been shown to lead to sleep disruption in adult rodents (Irwin, Miller, Christian Gillin, Demodena, & Ehlers, 2000;Mukherjee, Kazerooni, & Simasko, 2008;Mukherjee & Simasko, 2009;Sanchez-Alavez, Benedict, Wills, & Ehlers, 2019;Sharma, Engemann, Sahota, & Thakkar, 2010;Veatch, 2006), and it has been suggested that both cholinergic and adenosinergic mechanisms in basal forebrain may in part be responsible for alcohol-induced sleep disruption in adults (Ehlers, Criado, Wills, Liu, & Crews, 2011;Sharma, Sahota, & Thakkar, 2017). However, few studies have investigated the mechanisms underlying the effects of adolescent alcohol exposure on sleep.…”

Section: Discussionmentioning

confidence: 99%

Adolescent alcohol exposure increases orexin-A/hypocretin-1 in the anterior hypothalamus

Amodeo

Wills

et al. 2020

Alcohol

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Section: Discussionmentioning

confidence: 99%

Adolescent alcohol exposure increases orexin-A/hypocretin-1 in the anterior hypothalamus

Amodeo

Wills

et al. 2020

Alcohol

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“…Vehicle (1% DMSO in ACSF; 50 nL/side) and/or melatonin (500 pmol/50 nL/side) microinjections were performed at the onset of active/dark period on subsequent days (counterbalanced). Microinjections were carried out as described previously . In brief, mouse was removed out of its cage, gently swaddled in a towel.…”

Section: Methodsmentioning

confidence: 99%

“…Microinjections were carried out as described previously. 58,61 In brief, mouse was removed out of its cage, gently swaddled in a towel. Stylus was removed, and the injector cannula (connected to a 0.5-μL Hamilton syringe [Hamilton, Reno, NV]) was gently inserted into the ipsilateral guide cannula.…”

Section: Melatonin Infusion In the Pfhmentioning

confidence: 99%

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

Sharma

Sahota

Thakkar

2018

Journal of Pineal Research

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Melatonin promotes sleep. However, the underlying mechanisms are unknown. Orexin neurons in the perifornical lateral hypothalamus (PFH) are pivotal for wake promotion. Does melatonin promote sleep by inhibiting orexin neurons? We used C57BL/6J mice and designed 4 experiments to address this question. Experiment 1 used double-labeled immunofluorescence and examined the presence of melatonin receptors on orexin neurons. Second, mice, implanted with bilateral guides targeted toward PFH and sleep-recording electrodes, were infused with melatonin (500 pmole/50 nL/side) at dark onset (onset of active period), and spontaneous bouts of sleep-wakefulness were examined. Third, mice, implanted with bilateral guides into the PFH, were infused with melatonin (500 pmole/50 nL/side) at dark onset and euthanized 2 hours later, to examine the activation of orexin neurons using c-Fos expression in orexin neurons. Fourth, mice, implanted with PFH bilateral guides and sleep-recording electrodes, were infused with melatonin receptor antagonist, luzindole (10 pmol/50 nL/side), at light onset (onset of sleep period), and spontaneous bouts of sleep-wakefulness were examined. Our results suggest that orexin neurons express MT1, but not MT2 receptors. Melatonin infusion into the PFH, at dark onset, site-specifically and significantly increased NREM sleep (43.7%, P = .003) and reduced wakefulness (12.3%, P = .013). Local melatonin infusion at dark onset inhibited orexin neurons as evident by a significant reduction (66%, P = .0004) in the number of orexin neurons expressing c-Fos. Finally, luzindole infusion-induced blockade of melatonin receptors in PFH at sleep onset significantly increased wakefulness (44.1%, P = .015). Based on these results, we suggest that melatonin may act via the MT1 receptors to inhibit orexin neurons and promote sleep.

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“…However, whether ChAT-IR reductions are responsible for the fragmentation of sleep found in adolescent ethanol exposed rats is currently unknown. A reasonable hypothesis is that adolescent alcohol exposure influences multiple sleep systems, as has been reported in adult animals exposed to ethanol (see (Ehlers et al 2013a;Ehlers et al 2013b;Sanchez-Alavez et al 2018;Sharma et al 2010;Sharma et al 2017;Thakkar et al 2010)).…”

Section: Discussionmentioning

confidence: 92%

PSPH-D-18-00526: Effect of a dual orexin receptor antagonist (DORA-12) on sleep and event-related oscillations in rats exposed to ethanol vapor during adolescence

et al. 2019

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Rationale-Sleep difficulties are one of the problems associated with adolescent binge drinking. However, the mechanisms underlying adolescent alcohol-associated sleep disturbances and potential targets for therapy remain under investigated. Orexin receptor antagonists may have therapeutic value in the treatment of insomnia, yet the use of this class of drugs in the treatment of sleep disturbances following adolescent alcohol exposure has not been studied.Objectives-This study employed a model whereby ethanol vapor exposure occurred for 5 weeks during adolescence (AIE), and waking event-related oscillations (EROs) and EEG sleep were subsequently evaluated in young adult rats. The ability of 2 doses (10, 30 mg/kg PO) of a Dual Orexin Receptor Antagonist (DORA-12) to modify sleep, EEG and EROs was investigated in AIE rats and controls.Results-Adolescent vapor exposure was found to produce a fragmentation of sleep, in young adults, that was partially ameliorated by DORA-12. DORA-12 also produced increases in delta and theta power in waking EROs recorded before sleep, and deeper sleep as indexed by increases in delta and theta power in the sleep EEG in both ethanol and control rats. Rats given DORA-12 also fell asleep faster than vehicle treated rats as measured by a dose dependent reduction in the latency to both the first slow wave and REM sleep episodes.Conclusions-This study showed that DORA-12 can affect the sleep disturbance that is associated with a history of adolescent ethanol exposure and also has several other sleeppromoting effects that are equivalent in both ethanol and control rats.

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Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption

Cited by 16 publications

References 45 publications

Adolescent alcohol exposure increases orexin-A/hypocretin-1 in the anterior hypothalamus

Adolescent alcohol exposure increases orexin-A/hypocretin-1 in the anterior hypothalamus

Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus

PSPH-D-18-00526: Effect of a dual orexin receptor antagonist (DORA-12) on sleep and event-related oscillations in rats exposed to ethanol vapor during adolescence

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