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Orexinergic modulation of serotonin neurons in the dorsal raphe of a diurnal rodent, Arvicanthis niloticus.
- Source :
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Hormones and behavior [Horm Behav] 2019 Nov; Vol. 116, pp. 104584. Date of Electronic Publication: 2019 Aug 31. - Publication Year :
- 2019
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Abstract
- The hypothalamic neuropeptide, orexin (or hypocretin), is implicated in numerous physiology and behavioral functions, including affective states such as depression and anxiety. The underlying mechanisms and neural circuits through which orexin modulates affective responses remain unclear. The objective of the present study was to test the hypothesis that the serotonin (5-HT) system of the dorsal raphe nucleus (DRN) is a downstream target through which orexin potentially manifests its role in affective states. Using a diurnal rodent, the Nile grass rat (Arvicanthis niloticus), we first characterized the expression of the orexin receptors OX1R and OX2R in the DRN using in situ hybridization. The results revealed distinct distributions of OX1R and OX2R mRNAs, with OX1R predominantly expressed in the dorsal and lateral wings of the DRN that are involved in affective processes, while OX2R was mostly found in the ventral DRN that is more involved in sensory-motor function. We next examined how the orexin-OX1R pathway regulates 5-HT in the DRN and some of its projection sites using a selective OX1R antagonist SB-334867 (10 mg/kg, i.p.). A single injection of SB-334867 decreased 5-HT-ir fibers within the anterior cingulate cortex (aCgC); five once-daily administrations of SB-334867 decreased 5-HT-ir not only in the aCgC but also in the DRN, oval bed nucleus of the stria terminalis (ovBNST), nucleus accumbens shell (NAcSh), and periaqueductal gray (PAG). HPLC analysis revealed that five once-daily administrations of SB-334867 did not affect 5-HT turnover to any of the five sites, although it increased the levels of both 5-HT and 5-HIAA in the NAcSh. These results together suggest that orexinergic modulation of DRN 5-HT neurons via OX1Rs may be one pathway through which orexin regulates mood and anxiety, as well as perhaps other neurobiological processes.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Anxiety metabolism
Depression metabolism
Dorsal Raphe Nucleus drug effects
Male
Neurons drug effects
Neuropeptides metabolism
Orexin Receptor Antagonists pharmacology
Orexin Receptors metabolism
Orexins metabolism
Periaqueductal Gray drug effects
Periaqueductal Gray metabolism
Rats
Serotonin metabolism
Dorsal Raphe Nucleus metabolism
Neurons metabolism
Orexins physiology
Rodentia physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-6867
- Volume :
- 116
- Database :
- MEDLINE
- Journal :
- Hormones and behavior
- Publication Type :
- Academic Journal
- Accession number :
- 31445011
- Full Text :
- https://doi.org/10.1016/j.yhbeh.2019.104584