Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions

Ramalingam Vetrivelan, Clifford B Saper, Patrick M Fuller Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Armodafinil is the pharmacologically active R-enantiomer of modafinil, a widely prescribed wake-promoting agent used to trea...

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Autores principales:	Vetrivelan R, Saper CB, Fuller PM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495
Acceso en línea:	https://doaj.org/article/807c77e309ec426f81816f0795968e3a
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spelling	oai:doaj.org-article:807c77e309ec426f81816f0795968e3a2021-12-02T05:06:06ZArmodafinil-induced wakefulness in animals with ventrolateral preoptic lesions1179-1608https://doaj.org/article/807c77e309ec426f81816f0795968e3a2014-05-01T00:00:00Zhttp://www.dovepress.com/armodafinil-induced-wakefulness-in-animals-with-ventrolateral-preoptic-a16635https://doaj.org/toc/1179-1608 Ramalingam Vetrivelan, Clifford B Saper, Patrick M Fuller Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Armodafinil is the pharmacologically active R-enantiomer of modafinil, a widely prescribed wake-promoting agent used to treat several sleep-related disorders including excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea/hypopnea syndrome. Remarkably, however, the neuronal circuitry through which modafinil exerts its wake-promoting effects remains unresolved. In the present study, we sought to determine if the wake-promoting effects of armodafinil are mediated, at least in part, by inhibiting the sleep-promoting neurons of the ventrolateral preoptic (VLPO) nucleus. To do so, we measured changes in waking following intraperitoneal administration of armodafinil (200 mg/kg) or the psychostimulant methamphetamine (1 mg/kg) in rats with cell-body specific lesion of the VLPO. Rats with histologically confirmed lesions of the VLPO demonstrated a sustained increase in wakefulness at baseline, but the increase in wakefulness following administration of both armodafinil and methamphetamine was similar to that of intact animals. These data suggest that armodafinil increases wakefulness by mechanisms that extend beyond inhibition of VLPO neurons. Keywords: EEG, sleep, orexin-saporin, methamphetamineVetrivelan RSaper CBFuller PMDove Medical PressarticlePsychiatryRC435-571Neurophysiology and neuropsychologyQP351-495ENNature and Science of Sleep, Vol 2014, Iss default, Pp 57-63 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495
spellingShingle	Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 Vetrivelan R Saper CB Fuller PM Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
description	Ramalingam Vetrivelan, Clifford B Saper, Patrick M Fuller Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA Abstract: Armodafinil is the pharmacologically active R-enantiomer of modafinil, a widely prescribed wake-promoting agent used to treat several sleep-related disorders including excessive daytime sleepiness associated with narcolepsy, shift work sleep disorder, and obstructive sleep apnea/hypopnea syndrome. Remarkably, however, the neuronal circuitry through which modafinil exerts its wake-promoting effects remains unresolved. In the present study, we sought to determine if the wake-promoting effects of armodafinil are mediated, at least in part, by inhibiting the sleep-promoting neurons of the ventrolateral preoptic (VLPO) nucleus. To do so, we measured changes in waking following intraperitoneal administration of armodafinil (200 mg/kg) or the psychostimulant methamphetamine (1 mg/kg) in rats with cell-body specific lesion of the VLPO. Rats with histologically confirmed lesions of the VLPO demonstrated a sustained increase in wakefulness at baseline, but the increase in wakefulness following administration of both armodafinil and methamphetamine was similar to that of intact animals. These data suggest that armodafinil increases wakefulness by mechanisms that extend beyond inhibition of VLPO neurons. Keywords: EEG, sleep, orexin-saporin, methamphetamine
format	article
author	Vetrivelan R Saper CB Fuller PM
author_facet	Vetrivelan R Saper CB Fuller PM
author_sort	Vetrivelan R
title	Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
title_short	Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
title_full	Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
title_fullStr	Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
title_full_unstemmed	Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
title_sort	armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/807c77e309ec426f81816f0795968e3a
work_keys_str_mv	AT vetrivelanr armodafinilinducedwakefulnessinanimalswithventrolateralpreopticlesions AT sapercb armodafinilinducedwakefulnessinanimalswithventrolateralpreopticlesions AT fullerpm armodafinilinducedwakefulnessinanimalswithventrolateralpreopticlesions
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Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions

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