Centrally Administered Orexin A Increases Motivation for Sweet Pellets in Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2005 Aug 3

PMID 16075284

Citations 44

Authors

A J Thorpe

J P Cleary

A S Levine

C M Kotz

Affiliations

Soon will be listed here.

Abstract

Rationale: Centrally administered orexin A induces both feeding and locomotion in rats. Thus, the feeding response following orexin A administration may be secondary to general increases in activity rather than a specific motivation to eat.

Objective: The aim of the study is to determine whether orexin A increases the motivation to eat.

Methods: The effect of orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol) on breakpoint was determined in male Sprague-Dawley rats with rostro-lateral hypothalamic cannulae under a progressive ratio of five schedule (PR5). The effect of orexin A (0, 31.25, 125, and 500 pmol) on pressing rate under a fixed ratio (20) schedule was obtained to analyze the time course of orexin-A-induced pressing. The effect of 24-h food deprivation on breakpoint under PR5 and the effect of orexin A (125 pmol) on free feeding (sweet pellets) and on open-field locomotor activity (0, 100, 500, and 1,000 pmol) were also tested.

Results: Orexin A significantly augmented free feeding of sweet pellets, open-field locomotor activity, rate of pressing (FR20 schedule), and breakpoint (PR5 schedule), although compared to 24-h deprivation, the effect of orexin A on breakpoint was mild. However, there was a differential dose response relationship and time course of stimulation between orexin A's effects on locomotion and lever pressing.

Conclusion: These data indicate that infusion of orexin A enhances free feeding by enhancing and possibly prolonging motivation to eat.

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References

Sunter D, Morgan I, Edwards C, Dakin C, Murphy K, Gardiner J . Orexins: effects on behavior and localisation of orexin receptor 2 messenger ribonucleic acid in the rat brainstem. Brain Res. 2001; 907(1-2):27-34. DOI: 10.1016/s0006-8993(01)02344-7. View

Sahu A . Interactions of neuropeptide Y, hypocretin-I (orexin A) and melanin-concentrating hormone on feeding in rats. Brain Res. 2002; 944(1-2):232-8. DOI: 10.1016/s0006-8993(02)02941-4. View

Guan J, Saotome T, Wang Q, Funahashi H, Hori T, Tanaka S . Orexinergic innervation of POMC-containing neurons in the rat arcuate nucleus. Neuroreport. 2001; 12(3):547-51. DOI: 10.1097/00001756-200103050-00023. View

Zhang M, Balmadrid C, Kelley A . Nucleus accumbens opioid, GABaergic, and dopaminergic modulation of palatable food motivation: contrasting effects revealed by a progressive ratio study in the rat. Behav Neurosci. 2003; 117(2):202-11. DOI: 10.1037/0735-7044.117.2.202. View

Jewett D, Cleary J, Levine A, Schaal D, Thompson T . Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior. Psychopharmacology (Berl). 1995; 120(3):267-71. DOI: 10.1007/BF02311173. View

Espana R, Plahn S, Berridge C . Circadian-dependent and circadian-independent behavioral actions of hypocretin/orexin. Brain Res. 2002; 943(2):224-36. DOI: 10.1016/s0006-8993(02)02653-7. View

Yamanaka A, Kunii K, Nambu T, Tsujino N, Sakai A, Matsuzaki I . Orexin-induced food intake involves neuropeptide Y pathway. Brain Res. 2000; 859(2):404-9. DOI: 10.1016/s0006-8993(00)02043-6. View

Hagan J, Leslie R, Patel S, Evans M, Wattam T, Holmes S . Orexin A activates locus coeruleus cell firing and increases arousal in the rat. Proc Natl Acad Sci U S A. 1999; 96(19):10911-6. PMC: 17982. DOI: 10.1073/pnas.96.19.10911. View

Jain M, Horvath T, Kalra P, Kalra S . Evidence that NPY Y1 receptors are involved in stimulation of feeding by orexins (hypocretins) in sated rats. Regul Pept. 2000; 87(1-3):19-24. DOI: 10.1016/s0167-0115(99)00102-0. View

10.

Nishino S, Ripley B, Overeem S, Lammers G, Mignot E . Hypocretin (orexin) deficiency in human narcolepsy. Lancet. 2000; 355(9197):39-40. DOI: 10.1016/S0140-6736(99)05582-8. View

11.

Richardson N, Roberts D . Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods. 1996; 66(1):1-11. DOI: 10.1016/0165-0270(95)00153-0. View

12.

Horvath T, Diano S, van den Pol A . Synaptic interaction between hypocretin (orexin) and neuropeptide Y cells in the rodent and primate hypothalamus: a novel circuit implicated in metabolic and endocrine regulations. J Neurosci. 1999; 19(3):1072-87. PMC: 6782143. View

13.

Edwards C, Abusnana S, Sunter D, Murphy K, Ghatei M, Bloom S . The effect of the orexins on food intake: comparison with neuropeptide Y, melanin-concentrating hormone and galanin. J Endocrinol. 1999; 160(3):R7-12. DOI: 10.1677/joe.0.160r007. View

14.

Muroya S, Funahashi H, Yamanaka A, Kohno D, Uramura K, Nambu T . Orexins (hypocretins) directly interact with neuropeptide Y, POMC and glucose-responsive neurons to regulate Ca 2+ signaling in a reciprocal manner to leptin: orexigenic neuronal pathways in the mediobasal hypothalamus. Eur J Neurosci. 2004; 19(6):1524-34. DOI: 10.1111/j.1460-9568.2004.03255.x. View

15.

Hodos W, Kalman G . Effects of increment size and reinforcer volume on progressive ratio performance. J Exp Anal Behav. 1963; 6:387-92. PMC: 1404462. DOI: 10.1901/jeab.1963.6-387. View

16.

Ida T, Nakahara K, Katayama T, Murakami N, Nakazato M . Effect of lateral cerebroventricular injection of the appetite-stimulating neuropeptide, orexin and neuropeptide Y, on the various behavioral activities of rats. Brain Res. 1999; 821(2):526-9. DOI: 10.1016/s0006-8993(99)01131-2. View

17.

Marsh D, Hollopeter G, Huszar D, Laufer R, Yagaloff K, Fisher S . Response of melanocortin-4 receptor-deficient mice to anorectic and orexigenic peptides. Nat Genet. 1999; 21(1):119-22. DOI: 10.1038/5070. View

18.

Yamanaka A, Sakurai T, Katsumoto T, Yanagisawa M, Goto K . Chronic intracerebroventricular administration of orexin-A to rats increases food intake in daytime, but has no effect on body weight. Brain Res. 1999; 849(1-2):248-52. DOI: 10.1016/s0006-8993(99)01905-8. View

19.

Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli R, Tanaka H . Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998; 92(5):1 page following 696. DOI: 10.1016/s0092-8674(02)09256-5. View

20.

Szekely M, Petervari E, Balasko M, Hernadi I, Uzsoki B . Effects of orexins on energy balance and thermoregulation. Regul Pept. 2002; 104(1-3):47-53. DOI: 10.1016/s0167-0115(01)00348-2. View