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Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions

Authors Vetrivelan R, Saper C, Fuller P

Received 17 August 2013

Accepted for publication 22 October 2013

Published 2 May 2014 Volume 2014:6 Pages 57—63

DOI https://doi.org/10.2147/NSS.S53132

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4


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


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