Journal of Chemical Neuroanatomy 23 (2002) 49 – 58 Localization of hypocretin-like immunoreactivity in the brain of the diurnal rodent, Aricanthis niloticus Colleen M. Novak *, H. Elliott Albers Center for Behaioral Neuroscience, Departments of Biology and Psychology, Georgia State Uniersity, Atlanta, GA 30303, USA Received 18 June 2001; received in revised form 27 August 2001; accepted 28 August 2001 Abstract The neuropeptide hypocretin (HCRT, also called orexin) acts in the brain to increase arousal and inhibit REM sleep. There is also substantial evidence that disruption of the hypocretin system results in narcolepsy. The distribution of HCRT + fibers in nocturnal animals is consistent with its role in arousal; fibers are concentrated in brain areas important in arousal and the inhibition of REM sleep. The distribution of HCRT-like immunoreactive (HCRT +) cells and fibers has been described in nocturnal but not diurnal rodents. We therefore examined the anatomical distribution of HCRT + cells and fibers in the diurnal murid rodent Aricanthis niloticus (unstriped Nile grass rat). Aricanthis niloticus were perfused and brain sections were collected through the forebrain and midbrain and processed for HCRT immunocytochemistry. Hypocretin-like immunopositive cell bodies were located in the lateral hypothalamus, dorsomedial hypothalamus, and perifornical area. The densest staining for HCRT + neuronal fibers was seen in the paraventricular thalamic nucleus, the locus coeruleus, and the raphe nuclei. The distribution of HCRT + cells and fibers is consistent with that found in other rodents such as rats and Syrian hamsters. Although the pattern of HCRT-like immunostaining for cells and fibers is similar in nocturnal rodents and diurnal A. niloticus, it will be important to compare the pattern of HCRT release, as well as activity of HCRT cells, between nocturnal and diurnal species. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Orexin; Nile grass rats; Sleep; Feeding; Narcolepsy www.elsevier.com/locate/jchemneu 1. Introduction Several neurotransmitter systems regulate or modu- late the sleep–wake cycle. In the last few years, how- ever, the importance of the hypocretin (HCRT, also called orexin) family of neuropeptides to the regulation of the daily sleep – wake cycle has become recognized (Sakurai et al., 1998; Kilduff and Peyron, 2000). Hypo- cretin 1 and 2 (which correspond to orexin A and B) are associated with increased wakefulness and the inhi- bition of REM sleep (Chemelli et al., 1999; Siegel, 1999; Bourgin et al., 2000; Kilduff and Peyron, 2000; Thannickal et al., 2000; van den Pol, 2000). The sleep disorder narcolepsy, characterized by the inability to maintain wakefulness, is linked with the absence of functional HCRT or its receptors in narcoleptic dogs (Lin et al., 1999) and humans (Nishino et al., 2000; Thannickal et al., 2000). Similarly, knockout mice lack- ing either HCRT or its receptors show a narcolepsy-like behavioral arrest (Chemelli et al., 1999). In addition to modulating the sleep – wake cycle, hypocretin also in- creases food intake (Sakurai et al., 1998; Haynes et al., 1999; Sweet et al., 1999; Taheri et al., 2000a) and alters sympathetic and cardiovascular function (Samson et al., 1999; Shirasaka et al., 1999; Dun et al., 2000). The brain distribution of HCRT-immunoreactive (HCRT +) cells and fibers has been described in ro- dents, including rats (Peyron et al., 1998; Chen et al., 1999; Cutler et al., 1999; Date et al., 1999; Nambu et al., 1999; Risold et al., 1999) and Syrian hamsters (Mintz et al., 2001), as well as in humans (Moore et al., 2001). In these species, hypocretin-containing cells are * Corresponding author. Tel.: +1-404-651-0343; fax: +1-404-641- 3929. E-mail address: biocmn@panther.gsu.edu (C.M. Novak). 0891-0618/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0891-0618(01)00144-2