Artículo
Abstract:
Feeding behavior can be divided into appetitive and consummatory phases, differing in neural substrates and effects of deprivation. Opioids play an important role in the appetitive aspects of feeding, but they also have acute stimulatory effects on food consumption. Because the opioid peptide β-endorphin is co-synthesized and released with melanocortins from proopiomelanocortin (POMC) neuronal terminals, we examined the physiological role of β-endorphin in feeding and energy homeostasis using a strain of mutant mice with a selective deficiency of β-endorphin. Male β-endorphin-deficient mice unexpectedly became obese with ad libitum access to rodent chow. Total body weight increased by 15% with a 50-100% increase in the mass of white fat. The mice were hyperphagic with a normal metabolic rate. Despite the absence of endogenous β-endorphin, the mutant mice did not differ from wild-type mice in their acute feeding responses to β-endorphin or neuropeptide Y administered intracerebroventricularly or naloxone administered intraperitoneally. Additional mice were studied using an operant behavioral paradigm to examine their acquisition of food reinforcers under increasing work demands. Food-deprived, β-endorphin-deficient male mice emitted the same number of lever presses under a progressive ratio schedule compared to wild-type mice. However, the mutant mice worked significantly less than did the wild-type mice for food reinforcers under nondeprived conditions. Controls for nonspecific effects on acquisition of conditioned learning, activity, satiety, and resistance to extinction revealed no genotype differences, supporting our interpretation that β-endorphin selectively affects a motivational component of reward behavior under nondeprived conditions. Therefore, we propose that β-endorphin may function in at least two primary modes to modulate feeding. In the appetitive phase, β-endorphin release increases the incentive value of food as a primary reinforcer. In contrast, it appears that endogenous β-endorphin may inhibit food consumption in parallel with melanocortins and that the orexigenic properties previously ascribed to it may actually be due to other classes of endogenous opioid peptides.
Registro:
| Documento: | Artículo |
| Título: | State-dependent modulation of feeding behavior by proopiomelanocortin-derived β-endorphin |
| Autor: | Low, M.J.; Hayward, M.D.; Appleyard, S.M.; Rubinstein, M. |
| Filiación: | Vollum Institute, Oregon Health and Science University, Portland, OR 97239-3098, United States Dept. of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239-3098, United States Inst. Invest. Ing. Genet. Biol. M., Dept. of Physiol./Molec./Cell. Biol., University of Buenos Aires, Buenos Aires, 1428, Argentina |
| Palabras clave: | Deprivation state; Hyperphagia; Knockout mice; Metabolic rate; Motivation; Operant conditioning; Opioid peptides; Reinforcer; Sexual dimorphism; β-endorphin; beta endorphin; melanocortin; naloxone; neuropeptide Y; opiate peptide; proopiomelanocortin; adolescent; animal experiment; animal tissue; appetite; conference paper; controlled study; energy balance; feeding behavior; female; food deprivation; food intake; hormonal regulation; hyperphagia; instrumental conditioning; intracerebroventricular drug administration; intraperitoneal drug administration; knockout mouse; male; metabolic rate; motivation; mouse; nonhuman; obesity; reinforcement; sex difference; state dependent learning; white adipose tissue; Animalia; Rodentia |
| Año: | 2003 |
| Volumen: | 994 |
| Página de inicio: | 192 |
| Página de fin: | 201 |
| DOI: | http://dx.doi.org/10.1111/j.1749-6632.2003.tb03180.x |
| Título revista: | Annals of the New York Academy of Sciences |
| Título revista abreviado: | Ann. New York Acad. Sci. |
| ISSN: | 00778923 |
| CODEN: | ANYAA |
| CAS: | beta endorphin, 59887-17-1; naloxone, 357-08-4, 465-65-6; neuropeptide Y, 82785-45-3, 83589-17-7; proopiomelanocortin, 66796-54-1 |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00778923_v994_n_p192_Low |
Referencias:
- Morley, J.E., Neuropeptide regulation of appetite and weight (1987) Endocr. Rev., 8, pp. 256-287
- Glass, M.J., Billington, C.J., Levine, A.S., Opioids and food intake: Distributed functional neural pathways? (1999) Neuropeptides, 33, pp. 360-368
- Van Ree, J.M., Gerrits, M.A., Vanderschuren, L.J., Opioids, reward, and addiction: An encounter of biology, psychology, and medicine (1999) Pharmacol. Rev., 51, pp. 341-396
- Trujillo, K.A., Belluzzi, J.D., Stein, L., Opiate antagonists and self-stimulation: Extinction-like response patterns suggest selective reward deficit (1989) Brain Res., 492, pp. 15-28
- Belluzzi, J.D., Stein, L., Enkephaline may mediate euphoria and drive-reduction reward (1977) Nature, 266, pp. 556-558
- Reisine, T., Pasternak, G.W., Opioid analgesics and antagonists (1996) Goodman and Gilman's Pharmacologic Basis of Therapeutics, pp. 521-555. , J.G. Hardman, A.G. Gilman & L.E. Limbird, Eds. McGraw-Hill. New York
- Mucha, R.F., Herz, A., Motivational properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning (1985) Psychopharmacology, 86, pp. 274-280. , Berlin
- Rubinstein, M., Absence of opioid stress-induced analgesia in mice lacking beta-endorphin by site-directed mutagenesis (1996) Proc. Natl. Acad. Sci. USA, 93, pp. 3995-4000
- Appleyard, S.M., A role for the endogenous opioid β-endorphin in energy homeostasis (2003) Endocrinology, 144, pp. 1753-1760
- Hodos, W., Progressive ratio as a measure of reward strength (1961) Science, 134, pp. 943-944
- Hayward, M.D., Low, M.J., The effect of naloxone on operant behavior for food reinforcers in DBA/2 mice (2001) Brain Res. Bull., 56, pp. 537-543
- Glass, M.J., The effect of naloxone on food-motivated behavior in the obese Zucker rat (1999) Psychopharmacology, 141, pp. 378-384. , Berlin
- Cleary, J., Naloxone effects on sucrose-motivated behavior (1996) Psychopharmacology, 126, pp. 110-114. , Berlin
- Rudski, J.M., Billington, C.J., Levine, A.S., Naloxone's effects on operant responding depend upon level of deprivation (1994) Pharmacol. Biochem. Behav., 49, pp. 377-383
- Nader, K., Bechara, A., Van Der Kooy, D., Neurobiological constraints on behavioral models of motivation (1997) Annu. Rev. Psychol., 48, pp. 85-114
- Hayward, M.D., Pintar, J.E., Low, M.J., Selective reward deficit in mice lacking beta-endorphin and enkephalin (2002) J. Neurosci., 22, pp. 8251-8258
- Kalra, S.P., Interacting appetite-regulating pathways in the hypothalamic regulation of body weight (1999) Endocr. Rev., 20, pp. 68-100
- Glass, M.J., Potency of naloxone's anorectic effect in rats is dependent on diet preference (1996) Am. J. Physiol., 271, pp. R217-R221
- Weldon, D.T., Effect of naloxone on intake of cornstarch, sucrose, and polycose diets in restricted and nonrestricted rats (1996) Am. J. Physiol., 270, pp. R1183-R1188
- Pritchard, L.E., Turnbull, A.V., White, A., Pro-opiomelanocortin processing in the hypothalamus: Impact on melanocortin signalling and obesity (2002) J. Endocrinol., 172, pp. 411-421
- Castro, M.G., Morrison, E., Post-translational processing of proopiomelanocortin in the pituitary and in the brain (1997) Crit. Rev. Neurobiol., 11, pp. 35-57
- Silva, R.M., Beta-endorphin-induced feeding: Pharmacological characterization using selective opioid antagonists and antisense probes in rats (2001) J. Pharmacol. Exp. Ther., 297, pp. 590-596
- Slugg, R.M., Effect of the mu-opioid agonist DAMGO on medial basal hypothalamic neurons in beta-endorphin knockout mice (2000) Neuroendocrinology, 72, pp. 208-217
- Mogil, J.S., Disparate spinal and supraspinal opioid antinociceptive responses in beta endorphin-deficient mutant mice (2000) Neuroscience, 101, pp. 709-717
Citas:
---------- APA ----------
Low, M.J., Hayward, M.D., Appleyard, S.M. & Rubinstein, M. (2003) . State-dependent modulation of feeding behavior by proopiomelanocortin-derived β-endorphin. Annals of the New York Academy of Sciences, 994, 192-201.http://dx.doi.org/10.1111/j.1749-6632.2003.tb03180.x
---------- CHICAGO ----------
Low, M.J., Hayward, M.D., Appleyard, S.M., Rubinstein, M. "State-dependent modulation of feeding behavior by proopiomelanocortin-derived β-endorphin" . Annals of the New York Academy of Sciences 994 (2003) : 192-201.http://dx.doi.org/10.1111/j.1749-6632.2003.tb03180.x
---------- MLA ----------
Low, M.J., Hayward, M.D., Appleyard, S.M., Rubinstein, M. "State-dependent modulation of feeding behavior by proopiomelanocortin-derived β-endorphin" . Annals of the New York Academy of Sciences, vol. 994, 2003, pp. 192-201.http://dx.doi.org/10.1111/j.1749-6632.2003.tb03180.x
---------- VANCOUVER ----------
Low, M.J., Hayward, M.D., Appleyard, S.M., Rubinstein, M. State-dependent modulation of feeding behavior by proopiomelanocortin-derived β-endorphin. Ann. New York Acad. Sci. 2003;994:192-201.http://dx.doi.org/10.1111/j.1749-6632.2003.tb03180.x
