Armodafinil promotes wakefulness and activates Fos in rat brain.
Modafinil increases waking and labeling of Fos, a marker of neuronal activation. In the present study, armodafinil, the R-enantiomer of racemic modafinil, was administered to rats at 30 or 100 mg/kg i.p. about 5 h after lights on (circadian time 5 and near the midpoint of the sleep phase of the sleep:wake cycle) to assess its effects on sleep/wake activity and Fos activation. Armodafinil at 100 mg/kg increased wakefulness for 2 h, while 30 mg/kg armodafinil only briefly increased wakefulness. Armodafinil (30 and 100 mg/kg) also increased latencies to the onset of sleep and motor activity. Armodafinil had differential effects in increasing neuronal Fos immunolabeling 2 h after administration. Armodafinil at 100 mg/kg increased numbers of Fos-labeled neurons in striatum and anterior cingulate cortex, without affecting nucleus accumbens. Armodafinil at 30 mg/kg only increased numbers of light Fos-labeled neurons in the anterior cingulate cortex. In brainstem arousal centers, 100 mg/kg armodafinil increased numbers of Fos-labeled neurons in the tuberomammillary nucleus, pedunculopontine tegmentum, laterodorsal tegmentum, locus coeruleus, and dorsal raphe nucleus. Fos activation of these brainstem arousal centers, as well as of the cortex and striatum, is consistent with the observed arousal effects of armodafinil.
Fiocchi
Elaine M
EM
Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA.
Lin
Yin-Guo
YG
Aimone
Lisa
L
Gruner
John A
JA
Flood
Dorothy G
DG
D000818:Animals; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D000077408:Modafinil; D009043:Motor Activity / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014851:Wakefulness / Q000187:drug effects*
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D016760:Proto-Oncogene Proteins c-fos; D000077408:Modafinil