Orexins: effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem.
The orexins are neuropeptides originally reported to be involved in the stimulation of food intake. However, analysis of orexin immunoreactive fibres have revealed the densest innervation in brain sites involved in arousal and sleep-wake control, notably the noradrenergic locus coeruleus, an area that also expresses orexin receptor 1 (OX1R) messenger RNA (mRNA). We report here that, in the rat, a single intracerebroventricular injection of orexin A (1 and 3 nmol) or orexin B (3 nmol), during the early light phase, did not increase food intake over the first 4 h postinjection. However, the frequency of active behaviors such as grooming, rearing, burrowing and locomotion increased. Feeding behavior and food intake subsequently decreased over the following 20 h (4-24 h postinjection period) in the orexin A 3 nmol injected group whilst the frequency of inactive behavior (still or asleep) in this group increased. Using riboprobes, we performed in situ hybridization histochemistry to map the distribution of orexin receptor 2 (OX2R) mRNA within the rat brainstem. We report here, for the first time, the presence of OX2R mRNA in the nucleus of the solitary tract and the lateral reticular field (LRt). The LRt is a brainstem site that, amongst other functions, is implicated in attention and wakefulness. This distribution of OX2R and the effects on behavior support recent reports that the orexins might modulate central nervous system arousal and sleep-wake mechanisms rather than exclusively being involved in the control of food intake.
Sunter
D
D
ICSM Endocrine Unit, Imperial College School of Medicine, 6th Floor Commonwealth Building, Hammersmith Hospital, Du Cane Road, W12 0NN, 0NN, London, UK.
Morgan
I
I
Edwards
C M
CM
Dakin
C L
CL
Murphy
K G
KG
Gardiner
J
J
Taheri
S
S
Rayes
E
E
Bloom
S R
SR
D000818:Animals; D001066:Appetite / Q000187:drug effects* / Q000502:physiology; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects*; D001931:Brain Mapping; D001933:Brain Stem / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000528:radiation effects; D006120:Grooming / Q000187:drug effects; D007031:Hypothalamus / Q000502:physiology; D017403:In Situ Hybridization; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008027:Light; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D064446:Orexin Receptors; D000068797:Orexins; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D012890:Sleep / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D002352:Carrier Proteins; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide