Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat

Haynes, Andrea; Jackson, Brian A.; Overend, Philip; Buckingham, Robin E.; Wilson, Shelagh; Tadayyon, Mohammad; Arch, Jonathan R.S.

doi:10.1016/s0196-9781(99)00105-9

Cited by 281 publications

(168 citation statements)

References 34 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…On the other hand, the Hcrt projections to the NTS may function to modulate the activity of visceral afferents and/or to provide a general activation of the parasympathetic system during the digestive and absorptive phases of ingestion. However, it is now clear that orexin systems are not only involved in ingestive behaviors, but also exert an effect on a variety of physiological mechanisms involved in homeostasis (3,13,19,21,23,25,42,44,45,48). Therefore, it is possible that orexigenic pathways may function to adjust cardiovascular responses to activation of these different homeostatic mechanisms (10,12,15,33,42).…”

Section: Discussionmentioning

confidence: 99%

“…Although both Hcrt-1 and -2 have been shown to have similar physiological effects when administered centrally, Hcrt-1 appears to exert a more potent effect on most of these physiological variables (10,12,33,42,47). Hcrt-1 injections into the brain have been shown to increase feeding and drinking behaviors; produce sleep, wakefulness, and arousal disturbances; produce analgesia; activate the hypothalamic-pituitary axis; elicit gastric acid secretion; and alter temperature regulating mechanisms (3,14,19,21,23,25,42,44,45,48). Hcrt-1 neurons have been shown to contribute to an extensive innervation of forebrain, brain stem, and spinal cord structures (10,33,42,46,47), and receptors to Hcrt-1 have been demonstrated throughout the neuraxis (28).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

Oliveira

Rosas‐Arellano

Solano-Flores

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

lar effects of hypocretin-1 in nucleus of the solitary tract. Am J Physiol Heart Circ Physiol 284: H1369-H1377, 2003. First published December 12, 2002 10.1152/ajpheart.00877.2002Experiments were done in male Wistar rats to investigate the effects of microinjection of hypocretin-1 (Hcrt-1) into the nucleus of the solitary tract (NTS) on mean arterial pressure (MAP), heart rate (HR), and the baroreflex. In the first series, the distribution of Hcrt-1-like immunoreactivity (Ir) was mapped within the region of NTS. Hcrt-1 Ir was found throughout the NTS region, predominantly within the caudal dorsolateral (Slt), medial (Sm), and interstitial subnuclei of the NTS. In the second series, in ␣-chloralose or urethaneanesthetized rats, microinjection of Hcrt-1 (0.5-5 pmol) into the caudal NTS elicited a dose-dependent decrease in MAP and HR. A mapping of the caudal NTS region showed that the largest depressor and bradycardia responses elicited by Hcrt-1 were from sites in the Slt and Sm. In addition, doses Ͼ2.5 pmol at a small number of sites localized to the caudal commissural nucleus of NTS elicited pressor and tachycardia responses. Intravenous administration of the muscarinic receptor blocker atropine methyl bromide abolished the bradycardia response and attenuated the depressor response, whereas subsequent administration of the nicotinic receptor blocker hexamethonium bromide abolished the remaining MAP response. Finally, microinjection of Hcrt-1 into the NTS significantly potentiated the reflex bradycardia to activation of arterial baroreceptors as a result of increasing MAP by systemic injections of phenylephrine (2-4 g/kg). These results suggest that Hcrt-1 in the NTS activates neuronal circuits that increases vagal activity to the heart, inhibits sympathetic activity to the heart and vasculature, and alters the excitability of NTS neuronal circuits that reflexly control the circulation.orexin-A; blood pressure; baroreceptor reflex; brain stem; ingestive behavior HYPOCRETIN (Hcrt) neuropeptides have been recently shown to be almost exclusively expressed within neurons of the lateral and perifornical hypothalamic areas (30,33,35,47,49). These peptides, Hcrt-1, a 33 amino-acid peptide with an NH 2 -terminal pyrogutalmyl residue, and Hcrt-2, a 28 amino acid peptide with a COOH-terminal amide (35), are de-

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

Oliveira

Rosas‐Arellano

Solano-Flores

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Orexins, particularly orexin A, powerfully stimulate food intake after intracerebroventricular administration to sated or fasted rats (Sakurai et al, 1998 andHaynes et al, 1999), as well as having effects on wakefulness, pleasure and reward pathways and hormone secretion (Ganjavi HaS, 2007). On the other hand, fasting markedly up-regulates orexin mRNA expression in the LHA, further supporting its important role in appetite regulation (Sakurai et al, 1998).…”

Section: Introductionmentioning

confidence: 93%

Y4 receptors and pancreatic polypeptide regulate food intake via hypothalamic orexin and brain-derived neurotropic factor dependent pathways

et al. 2010

View full text Add to dashboard Cite

Gut-derived peptides are known to regulate food intake by activating specific receptors in the brain, but the target nuclei and neurons influenced are largely unknown. Here we show that peripherally administered pancreatic polypeptide (PP) stimulates neurons in key nuclei of the hypothalamus critical for appetite and satiety regulation. In the lateral hypothalamic area (LHA), also known as the feeding center, neurons expressing the orexigenic neuropeptide orexin co-localize with the early neuronal activation marker c-Fos upon i.p. injection of PP into mice. In the ventromedial hypothalamus (VMH), also known as the satiety center, neurons activated by PP, as indicated by induction of c-Fos immunoreactivity, express the anorexigenic brain-derived neurotrophic factor (BDNF). Activation of neurons in the LHA and VMH in response to PP occurs via a Y4 receptor-dependent process as it is not seen in Y4 receptor knockout mice. We further demonstrate that in response to i.p. PP, orexin mRNA expression in the LHA is down-regulated, with Y4 receptors being critical for this effect as it is not seen in Y4 receptor knockout mice, whereas BDNF mRNA expression is up-regulated in the VMH in response to i.p. PP in the fasted, but not in the non-fasted state. Taken together these data suggest that PP can regulate food intake by suppressing orexigenic pathways by down-regulation of orexin and simultaneously increasing anorexigenic pathways by upregulating BDNF.

show abstract

“…The hypocretinergic system has been suggested to play a role in a variety of physiological processes, most of which involve activation of the somatomotor system (Pu et al, 1998;Chemelli et al, 1999;Haynes et al, 1999;Lin et al, 1999;Siegel, 1999;Tamura et al, 1999;Kilduff and Peyron, 2000;Sutcliffe and de Lecea, 2000;Lin et al, 2002;Wu et al, 2002). Hcrtcontaining neurons project to regions that are involved in the generation of somatomotor activity Zhang et al, 2002) that provides a foundation for the concept that Hcrt is involved in the control of motor processes.…”

Section: Considerations Of the Physiological Significance Of Hcrt Actmentioning

confidence: 99%

Hypocretinergic Control of Spinal Cord Motoneurons

Yamuy

Fung²,

Xi³

et al. 2004

Journal of Neuroscience

View full text Add to dashboard Cite

Hypocretinergic (orexinergic) neurons in the lateral hypothalamus project to motor columns in the lumbar spinal cord. Consequently, we sought to determine whether the hypocretinergic system modulates the electrical activity of motoneurons. Using in vivo intracellular recording techniques, we examined the response of spinal motoneurons in the cat to electrical stimulation of the lateral hypothalamus. In addition, we examined the membrane potential response to orthodromic stimulation and intracellular current injection before and after both hypothalamic stimulation and the juxtacellular application of hypocretin-1. It was found that (1) hypothalamic stimulation produced a complex sequence of depolarizing-hyperpolarizing potentials in spinal motoneurons; (2) the depolarizing potentials decreased in amplitude after the application of SB-334867, a hypocretin type 1 receptor antagonist; (3) the EPSP induced by dorsal root stimulation was not affected by the application of SB-334867; (4) subthreshold stimulation of dorsal roots and intracellular depolarizing current steps produced spike potentials when applied in concert to stimulation of the hypothalamus or after the local application of hypocretin-1; (5) the juxtacellular application of hypocretin-1 induced motoneuron depolarization and, frequently, high-frequency discharge; (6) hypocretin-1 produced a significant decrease in rheobase (36%), membrane time constant (16.4%), and the equalizing time constant (23.3%); (7) in a small number of motoneurons, hypocretin-1 produced an increase in the synaptic noise; and (8) the input resistance was not affected after hypocretin-1. The juxtacellular application of vehicle (saline) and denatured hypocretin-1 did not produce changes in the preceding electrophysiological properties.We conclude that hypothalamic hypocretinergic neurons are capable of modulating the activity of lumbar motoneurons through presynaptic and postsynaptic mechanisms. The lack of hypocretin-induced facilitation of motoneurons may be a critical component of the pathophysiology of cataplexy.

show abstract

Effects of single and chronic intracerebroventricular administration of the orexins on feeding in the rat

Cited by 281 publications

References 34 publications

Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

Cardiovascular effects of hypocretin-1 in nucleus of the solitary tract

Y4 receptors and pancreatic polypeptide regulate food intake via hypothalamic orexin and brain-derived neurotropic factor dependent pathways

Hypocretinergic Control of Spinal Cord Motoneurons

Contact Info

Product

Resources

About