A role for lateral hypothalamic orexin neurons in reward seeking
Abstract
The lateral hypothalamus is a brain region historically implicated in reward and motivation, but the identity of the neurotransmitters involved are unknown. The orexins (or hypocretins) are neuropeptides recently identified as neurotransmitters in lateral hypothalamus neurons. Although knockout and transgenic overexpression studies have implicated orexin neurons in arousal and sleep, these cells also project to reward-associated brain regions, including the nucleus accumbens and ventral tegmental area. This indicates a possible role for these neurons in reward function and motivation, consistent with previous studies implicating these neurons in feeding. Here we show that activation of lateral hypothalamus orexin neurons is strongly linked to preferences for cues associated with drug and food reward. In addition, we show that chemical activation of lateral hypothalamus orexin neurons reinstates an extinguished drug-seeking behaviour. This reinstatement effect was completely blocked by prior administration of an orexin A antagonist. Moreover, administration of the orexin A peptide directly into the ventral tegmental area also reinstated drug-seeking. These data reveal a new role for lateral hypothalamus orexin neurons in reward-seeking, drug relapse and addiction.
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The nucleus accumbens shell is part of a neural loop including the lateral hypothalamus and the ventral tegmental area, with orexin neurons playing a key role.
“The nucleus accumbens shell is thereby part of a neural loop including the lateral hypothalamus and the ventral tegmental area, with orexin neurons playing a key role ([7](#B7), [22](#B22), [77](#B77), [98](#B98), [115](#B115), [125](#B125), [175](#B175), [199](#B199)).”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [77]
Lateral hypothalamic neurons expressing orexin and other transmitters such as neurotensin provide modulatory input to midbrain dopamine neurons.
“Recent investigations show that lateral hypothalamic neurons expressing orexin ([77](#B77), [199](#B199)) and other transmitters such as neurotensin ([101](#B101), [107](#B107)) provide modulatory input to midbrain dopamine neurons”
From Food reward, hyperphagia, and obesity (2011) · cites this paper as [77]
Cites
Sakurai, T., Amemiya, A., Ishii, M., Matsuzaki, I., Chemelli, R. M., Tanaka, H., Williams, S. C., Richardson, J. A., Kozlowski, G. P., Wilson, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80949-6 · Cited by 5,501 · see citing works
The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity
de Lecea, L., Kilduff, T. S., Peyron, C., Gao, X.-B., Foye, P. E., Danielson, P. E., Fukuhara, C., Battenberg, E. L. F., Gautvik, V. T., Bartlett, F. S., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.322 · Cited by 3,878 · see citing works
Neurons containing hypocretin (orexin) project to multiple neuronal systems
Peyron, C., Tighe, D. K., van den Pol, A. N., de Lecea, L., Heller, H. C., Sutcliffe, J. G., & Kilduff, T. S. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09996.1998 · Cited by 3,466 · see citing works
Olds, J., & Milner, P. (1954) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0058775 · Cited by 3,176 · see citing works
Narcolepsy in orexin Knockout Mice
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)81973-x · Cited by 3,095 · see citing works
Brain Maps: Structure of the Rat Brain
Swanson, L. W. (1992) · Medical Entomology and Zoology · Cited by 1,851 · see citing works
Brain maps: structure of the rat brain
Guillery, R. W. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90187-q · Cited by 1,677 · see citing works
Differential expression of orexin receptors 1 and 2 in the rat brain
Marcus, J. N., Aschkenasi, C. J., Lee, C. E., Chemelli, R. M., Saper, C. B., Yanagisawa, M., & Elmquist, J. K. (2001) · Journal of Comparative Neurology · doi:10.1002/cne.1190 · Cited by 1,659 · see citing works
Hypothalamic control of food intake in rats and cats.
Anand, B. K., & Brobeck, J. R. (1951) · PubMed · Cited by 1,197 · see citing works
Distribution of orexin receptor mRNA in the rat brain
Trivedi, P. G., Yu, H., MacNeil, D. J., der Ploeg, L. H. T. V., & Guan, X.-M. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01266-6 · Cited by 979 · see citing works
Neurobiology of relapse to heroin and cocaine seeking: a review
Shalev, U., Grimm, J. W., & Shaham, Y. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.1.1 · Cited by 880 · see citing works
Herrera, D., & Robertson, H. A. (1996) · Progress in Neurobiology · doi:10.1016/s0301-0082(96)00021-4 · Cited by 713 · see citing works
Fos Expression in Orexin Neurons Varies with Behavioral State
Estabrooke, I. V., McCarthy, M. T., Ko, E., Chou, T. C., Chemelli, R. M., Yanagisawa, M., Saper, C. B., & Scammell, T. E. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01656.2001 · Cited by 654 · see citing works
Excitation of Ventral Tegmental Area Dopaminergic and Nondopaminergic Neurons by Orexins/Hypocretins
Korotkova, T. M., Sergeeva, O. A., Eriksson, K. S., Haas, H. L., & Brown, R. E. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00007.2003 · Cited by 583 · see citing works
Fadel, J. R., & Deutch, A. Y. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00017-9 · Cited by 503 · see citing works
Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal
Georgescu, D., Zachariou, V., Barrot, M., Mieda, M., Willie, J. T., Eisch, A. J., Yanagisawa, M., Nestler, E. J., & DiLeone, R. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03106.2003 · Cited by 373 · see citing works
Baldo, B. A., Daniel, R. A., Berridge, C. W., & Kelley, A. E. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10783 · Cited by 346 · see citing works
A selective orexin-1 receptor antagonist reduces food consumption in male and female rats
Haynes, A. C., Jackson, B., Chapman, H., Tadayyon, M., Johns, A., Porter, R. A., & Arch, J. R. S. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00199-3 · Cited by 338 · see citing works
SB‐334867‐A: the first selective orexin‐1 receptor antagonist
Smart, D., Sabido-David, C., Brough, S. J., Jewitt, F., Johns, A., Porter, R. A., & Jerman, J. C. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703953 · Cited by 308 · see citing works
Augmentation of drug reward by chronic food restriction
Carr, K. D. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00759-x · Cited by 300 · see citing works
Hypocretin (OREXIN): Role in Normal Behavior and Neuropathology
Siegel, J. M. (2004) · Annual Review of Psychology · doi:10.1146/annurev.psych.55.090902.141545 · Cited by 247 · see citing works
Rodgers, R. J., Halford, J. C. G., de Souza, R. L. N., de Souza, A. L. C., Piper, D. C., Arch, J. R. S., Upton, N., Porter, R. A., Johns, A., & Blundell, J. E. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01518.x · Cited by 230 · see citing works
Lateral hypothalamic neuropeptides in reward and drug addiction
Dileone, R., Georgescu, D., & Nestler, E. J. (2003) · Life Sciences · doi:10.1016/s0024-3205(03)00408-9 · Cited by 220 · see citing works
Critical Role for Ventral Tegmental Glutamate in Preference for a Cocaine-Conditioned Environment
Harris, G. C., & Aston‐Jones, G. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300011 · Cited by 163 · see citing works
Self-citationEspaña, R. A., Valentino, R. J., & Berridge, C. W. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00334-8 · Cited by 142 · see citing works
Baldo, B. A., Gual‐Bonilla, L., Sijapati, K. S., Daniel, R. A., Landry, C. F., & Kelley, A. E. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03093.x · Cited by 130 · see citing works
Orexin Neurons Express a Functional Pancreatic Polypeptide Y4 Receptor
Campbell, R. E., Smith, M. S., Allen, S. E., Grayson, B. E., ffrench‐Mullen, J. M. H., & Grove, K. L. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01487.2003 · Cited by 108 · see citing works
Stress or drug priming induces reinstatement of extinguished conditioned place preference
Wang, B., Luo, F., Zhang, W., & Han, J.-S. (2000) · Neuroreport · doi:10.1097/00001756-200008210-00034 · Cited by 107 · see citing works
Bevins, R. A., Besheer, J., Palmatier, M. I., Jensen, H. C., Pickett, K. S., & Eurek, S. E. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00326-6 · Cited by 98 · see citing works
Harris, G. C., & Aston‐Jones, G. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300037 · Cited by 92 · see citing works
Self-citationAmygdala Subsystems and Control of Feeding Behavior by Learned Cues
Petrovich, G. D., & Gallagher, M. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07086.x · Cited by 87 · see citing works
Harris, G. C., & Aston‐Jones, G. (2002) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300122 · Cited by 74 · see citing works
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The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077 · see citing works
Ikemoto, S. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.004 · Cited by 1,477 · see citing works
Saper, C. B., Fuller, P. M., Pedersen, N. P., Lu, J., & Scammell, T. E. (2010) · Neuron · doi:10.1016/j.neuron.2010.11.032 · Cited by 1,404 · see citing works
The metabolic consequences of sleep deprivation
Knutson, K. L., Spiegel, K., Penev, P., & Van Cauter, E. (2007) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2007.01.002 · Cited by 1,365 · see citing works
Avena, N. M., Rada, P., & Hoebel, B. G. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.04.019 · Cited by 1,358 · see citing works
Tzschentke, T. M. (2007) · Addiction Biology · doi:10.1111/j.1369-1600.2007.00070.x · Cited by 1,336 · see citing works
The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness
Sakurai, T. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2092 · Cited by 1,276 · see citing works
“Liking” and “wanting” food rewards: Brain substrates and roles in eating disorders
Berridge, K. C. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.02.044 · Cited by 1,147 · see citing works
A Role for Brain Stress Systems in Addiction
Koob, G. F. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.012 · Cited by 1,056 · see citing works
Cortico-Basal Ganglia Reward Network: Microcircuitry
Sesack, S. R., & Grace, A. A. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2009.93 · Cited by 985 · see citing works
Green, C. B., Takahashi, J. S., & Bass, J. (2008) · Cell · doi:10.1016/j.cell.2008.08.022 · Cited by 902 · see citing works
The tempted brain eats: Pleasure and desire circuits in obesity and eating disorders
Berridge, K. C., Ho, C.-Y., Richard, J. M., & DiFeliceantonio, A. G. (2010) · Brain Research · doi:10.1016/j.brainres.2010.04.003 · Cited by 873 · see citing works
<i>Associations between Sleep Loss and Increased Risk of Obesity and Diabetes</i>
Knutson, K. L., & Van Cauter, E. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1417.033 · Cited by 810 · see citing works
Sleep curtailment is accompanied by increased intake of calories from snacks
Nedeltcheva, A. V., Kilkus, J. M., Imperial, J., Kasza, K., Schoeller, D. A., & Penev, P. D. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26574 · Cited by 717 · see citing works
Borgland, S. L., Taha, S. A., Sarti, F., Fields, H. L., & Bonci, A. (2006) · Neuron · doi:10.1016/j.neuron.2006.01.016 · Cited by 718 · see citing works
Homeostatic and hedonic signals interact in the regulation of food intake
Lutter, M., & Nestler, E. J. (2009) · The Journal of Nutrition · doi:10.3945/jn.108.097618 · Cited by 614 · see citing works
Menstrual cycle phase modulates reward-related neural function in women
Dreher, J.-C., Schmidt, P. J., Kohn, P., Furman, D., Rubinow, D., & Berman, K. F. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605569104 · Cited by 567 · see citing works
Hypocretin/orexin overexpression induces an insomnia-like phenotype in zebrafish
Prober, D. A., Rihel, J., Onah, A. A., Sung, R.-J., & Schier, A. F. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4332-06.2006 · Cited by 508 · see citing works
Role for hypocretin in mediating stress-induced reinstatement of cocaine-seeking behavior
Boutrel, B., Kenny, P. J., Specio, S. E., Martin-Fardon, R., Markou, A., Koob, G. F., & de Lecea, L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507480102 · Cited by 520 · see citing works
A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse
Xue, Y.-X., Luo, Y.-X., Wu, P., Shi, H.-S., Xue, L.-F., Chen, C., Zhu, W.-L., Ding, Z.-B., Bao, Y.-P., Shi, J., et al. (2012) · Science · doi:10.1126/science.1215070 · Cited by 511 · see citing works
The neurocircuitry of addiction: an overview
Feltenstein, M. W., & See, R. E. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.51 · Cited by 421 · see citing works
Nieh, E. H., Vander Weele, C. M., Matthews, G. A., Presbrey, K. N., Wichmann, R., Leppla, C. A., Izadmehr, E. M., & Tye, K. M. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.035 · Cited by 387 · see citing works
Overlapping Brain Circuits for Homeostatic and Hedonic Feeding
Rossi, M. A., & Stuber, G. D. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.021 · Cited by 415 · see citing works
Leinninger, G. M., Jo, Y.-H., Leshan, R. L., Louis, G. W., Yang, H., Barrera, J. G., Wilson, H., Opland, D. M., Faouzi, M. A., Gong, Y., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.06.011 · Cited by 412 · see citing works
The orexin system regulates alcohol-seeking in rats
Lawrence, A. J., Cowen, M. S., Yang, H., Chen, F., & Oldfield, B. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706789 · Cited by 392 · see citing works
Afferents to the GABAergic tail of the ventral tegmental area in the rat
Kaufling, J., Veinante, P., Pawlowski, S. A., Freund‐Mercier, M., & Barrot, M. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21983 · Cited by 347 · see citing works
An essential role for orexins in emergence from general anesthesia
Kelz, M. B., Sun, Y., Chen, J., Cheng Meng, Q., Moore, J. T., Veasey, S. C., Dixon, S., Thornton, M., Funato, H., & Yanagisawa, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707146105 · Cited by 341 · see citing works
Inactivation of the Interoceptive Insula Disrupts Drug Craving and Malaise Induced by Lithium
Contreras, M., Ceric, F., & Torrealba, F. (2007) · Science · doi:10.1126/science.1145590 · Cited by 297 · see citing works
Insular hypocretin transmission regulates nicotine reward
Hollander, J. A., Lu, Q., Cameron, M. D., Kamenecka, T. M., & Kenny, P. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808023105 · Cited by 296 · see citing works
Food reward, hyperphagia, and obesity
Berthoud, H.-R., Lenard, N. R., & Shin, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00028.2011 · Cited by 275 · see citing works
Zheng, H., Patterson, L. M., & Berthoud, H.-R. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3542-07.2007 · Cited by 248 · see citing works
Orexin Signaling Mediates the Antidepressant-Like Effect of Calorie Restriction
Lutter, M., Krishnan, V., Russo, S. J., Jung, S., McClung, C. A., & Nestler, E. J. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.5584-07.2008 · Cited by 234 · see citing works
Richards, J. K., Simms, J. A., Steensland, P., Taha, S. A., Borgland, S. L., Bonci, A., & Bartlett, S. E. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1136-5 · Cited by 234 · see citing works
Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity
Cason, A. M., Smith, R. J., Tahsili-Fahadan, P., Moorman, D. E., Sartor, G. C., & Aston-Jones, G. (2010) · Physiology & Behavior · doi:10.1016/j.physbeh.2010.03.009 · Cited by 229 · see citing works
Self-citationMultiple roles for orexin/hypocretin in addiction
Mahler, S. V., Smith, R. J., Moorman, D. E., Sartor, G. C., & Aston-Jones, G. (2012) · Progress in Brain Research · doi:10.1016/b978-0-444-59489-1.00007-0 · Cited by 215 · see citing works
Self-citationSmith, R. J., & Aston-Jones, G. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0191-3 · Cited by 206 · see citing works
Self-citationStaying awake for dinner: hypothalamic integration of sleep, feeding, and circadian rhythms
Saper, C. B. (2006) · Progress in Brain Research · doi:10.1016/s0079-6123(06)53014-6 · Cited by 178 · see citing works
Brain regulation of energy balance and body weight
Rui, L. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9261-9 · Cited by 168 · see citing works
Elman, I., Borsook, D., & Lukas, S. E. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301051 · Cited by 169 · see citing works
Richard, J. E., Anderberg, R. H., Göteson, A., Gribble, F. M., Reimann, F., & Skibicka, K. P. (2015) · PLOS ONE · doi:10.1371/journal.pone.0119034 · Cited by 168 · see citing works
Venniro, M., Caprioli, D., Zhang, M., Whitaker, L. R., Zhang, S., Warren, B. L., Cifani, C., Marchant, N. J., Yizhar, O., Bossert, J. M., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.024 · Cited by 162 · see citing works
Granular insular cortex inactivation as a novel therapeutic strategy for nicotine addiction
Forget, B., Pushparaj, A., & Le Foll, B. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.029 · Cited by 153 · see citing works
Yang, L., Zou, B., Xiong, X., Pascual, C., Xie, J., Malik, A., Xie, J., Sakurai, T., & Xie, X. (. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3200-12.2013 · Cited by 153 · see citing works
Balcita‐Pedicino, J. J., & Sesack, S. R. (2007) · Journal of Comparative Neurology · doi:10.1002/cne.21420 · Cited by 150 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
Hsu, D. T., & Price, J. L. (2009) · Journal of Comparative Neurology · doi:10.1002/cne.21934 · Cited by 127 · see citing works
Davis, J. F., Choi, D. L., & Benoit, S. C. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.08.004 · Cited by 129 · see citing works
Functional implications of glutamatergic projections to the ventral tegmental area
Geisler, S., & Wise, R. A. (2008) · Reviews in the Neurosciences · doi:10.1515/revneuro.2008.19.4-5.227 · Cited by 125 · see citing works
Modulation of taste responsiveness and food preference by obesity and weight loss
Berthoud, H.-R., & Zheng, H. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.04.004 · Cited by 123 · see citing works
Martin-Fardon, R., Zorrilla, E. P., Ciccocioppo, R., & Weiss, F. (2010) · Brain Research · doi:10.1016/j.brainres.2009.12.027 · Cited by 112 · see citing works
Nair, S. G., Adams-Deutsch, T., Epstein, D. H., & Shaham, Y. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.05.003 · Cited by 112 · see citing works
Anhedonia in depression symptomatology: appetite dysregulation and defective brain reward processing
Coccurello, R. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.112041 · Cited by 106 · see citing works
Modulation of the mesolimbic dopamine system by leptin
Opland, D. M., Leinninger, G. M., & Myers (2010) · Brain Research · doi:10.1016/j.brainres.2010.04.028 · Cited by 111 · see citing works
The neurobiology of appetite: hunger as addiction.
Dagher, A. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.69 · Cited by 108 · see citing works
Shining light on wakefulness and arousal
de Lecea, L., Carter, M. E., & Adamantidis, A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.032 · Cited by 103 · see citing works
Alcohol use disorders and ADHD.
Luderer, M., Ramos Quiroga, J. A., Faraone, S. V., Zhang-James, Y., & Reif, A. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.010 · Cited by 102 · see citing works
Brown, R. M., Khoo, S. Y.-S., & Lawrence, A. J. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713000333 · Cited by 101 · see citing works
Hunger and Satiety Gauge Reward Sensitivity
Cassidy, R. M., & Tong, Q. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00104 · Cited by 93 · see citing works
Chen, S. A., O'Dell, L. E., Hoefer, M. E., Greenwell, T. N., Zorrilla, E. P., & Koob, G. F. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301008 · Cited by 97 · see citing works
Neural and metabolic regulation of macronutrient intake and selection
Berthoud, H.-R., Münzberg, H., Richards, B. K., & Morrison, C. D. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000559 · Cited by 87 · see citing works
Hypocretin as a Hub for Arousal and Motivation
Tyree, S. M., Borniger, J. C., & de Lecea, L. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00413 · Cited by 83 · see citing works
Sleep and dreaming are for important matters
Perogamvros, L., Dang-Vu, T. T., Desseilles, M., & Schwartz, S. (2013) · Frontiers in Psychology · doi:10.3389/fpsyg.2013.00474 · Cited by 77 · see citing works
“Finally, the orexin neurons in the lateral hypothalamus, related to emotional processing and motivated behaviors (Harris et al., 2005; Schwartz et al., 2008; Ponz et al., 2010a,b; Thompson and Borgland, 2011), have occasional burst discharges during REM sleep of rodents (Mileykovskiy et al., 2005;…”
BackgroundSchmeichel, B. E., Barbier, E., Misra, K. K., Contet, C., Schlosburg, J. E., Grigoriadis, D., Williams, J. P., Karlsson, C., Pitcairn, C., Heilig, M., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2014.293 · Cited by 79 · see citing works
Morganstern, I., Chang, G., Barson, J. R., Ye, Z., Karatayev, O., & Leibowitz, S. F. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01161.x · Cited by 79 · see citing works
Huhn, A. S., Finan, P. H., Gamaldo, C. E., Hammond, A. S., Umbricht, A., Bergeria, C. L., Strain, E. C., & Dunn, K. E. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abn8238 · Cited by 79 · see citing works
Huang, H., Xu, Y., & van den Pol, A. N. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00740.2010 · Cited by 70 · see citing works
Tobacco dependence, the insular cortex and the hypocretin connection
Kenny, P. J. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.08.015 · Cited by 69 · see citing works
Brown, R. M., Short, J. L., & Lawrence, A. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015889 · Cited by 69 · see citing works
Bonci, A., & Borgland, S. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.024 · Cited by 64 · see citing works
Orexin-A Hyperphagia: Hindbrain Participation in Consummatory Feeding Responses
Baird, J.-P., Choe, A., Loveland, J. L., Beck, J., Mahoney, C. E., Lord, J. S., & Grigg, L. A. (2009) · Endocrinology · doi:10.1210/en.2008-0293 · Cited by 65 · see citing works
Overview of orexin/hypocretin system
Mieda, M., & Sakurai, T. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59489-1.00002-1 · Cited by 64 · see citing works
Zhou, Y., Proudnikov, D., Yuferov, V., & Kreek, M. J. (2010) · Brain Research · doi:10.1016/j.brainres.2009.11.015 · Cited by 58 · see citing works
Learning and the motivation to eat: forebrain circuitry.
Petrovich, G. D. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.04.059 · Cited by 57 · see citing works
LRb signals act within a distributed network of leptin‐responsive neurones to mediate leptin action
Leinninger, G. M., & Myers, M. G. (2008) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01784.x · Cited by 56 · see citing works
Glucose-Sensing in the Reward System
Koekkoek, L. L., Mul, J. D., & la Fleur, S. E. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00716 · Cited by 51 · see citing works
Brain control of energy homeostasis: implications for anti-obesity pharmacotherapy
Johansen, V. B. I., Petersen, J., Lund, J., Mathiesen, C. V., Fenselau, H., & Clemmensen, C. (2025) · Cell · doi:10.1016/j.cell.2025.06.010 · Cited by 53 · see citing works
Control of energy homeostasis by the lateral hypothalamic area
Rossi, M. A. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.05.010 · Cited by 50 · see citing works
Verty, A. N. A., Boon, W. M., Mallet, P. E., McGregor, I. S., & Oldfield, B. J. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06750.x · Cited by 39 · see citing works
Orexin (hypocretin) and addiction
Mehr, J. B., Bilotti, M. M., & James, M. H. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2021.09.002 · Cited by 40 · see citing works
McGinty, V. B., Hayden, B. Y., Heilbronner, S. R., Dumont, E. C., Graves, S. M., Mirrione, M. M., du Hoffmann, J., Sartor, G. C., España, R. A., Millan, E. Z., et al. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.07.036 · Cited by 36 · see citing works
(2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.03.012 · Cited by 34 · see citing works
Chung, H.-S., Kim, J.-G., Kim, J.-W., Kim, H.-W., & Yoon, B.-J. (2014) · Regulatory Peptides · doi:10.1016/j.regpep.2014.11.003 · Cited by 32 · see citing works
Hata, T., Chen, J., Ebihara, K., Date, Y., Ishida, Y., & Nakahara, D. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07808.x · Cited by 25 · see citing works
Flores‐Ramirez, F. J., Varodayan, F. P., Patel, R. R., Illenberger, J. M., Di Ottavio, F., Roberto, M., & Martin‐Fardon, R. (2023) · British Journal of Pharmacology · doi:10.1111/bph.16015 · Cited by 19 · see citing works
- Authors
- Harris, G. C., Wimmer, M., & Aston-Jones, G.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Harris, Glenda C.
- ORCID
- Wimmer, Mathieu
- Venue
- Nature
- Published
- 2005-08-14
- Volume
- 437
- Issue
- 7058
- Pages
- 556-559
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1966793802
- Cited by
- 1,311
- References
- 32
- Citations by year
- 2026: 20 · 2025: 41 · 2024: 48 · 2023: 45 · 2022: 61 · 2021: 52 · 2020: 54 · 2019: 47 · 2018: 80 · 2017: 60 · 2016: 76 · 2015: 69 · 2014: 76 · 2013: 84 · 2012: 85
- FWCI
- 21.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- orexin, lateral hypothalamus, drug-seeking behavior, food seeking, drug relapse, reinstatement, ventral tegmental area, reward, motivation, drug addiction, overeating, nucleus accumbens
- MeSH terms
- Orexins, Animals, Cues, Hypothalamus, Injections, Intraventricular, Male, Morphine, Neurons, Neuropeptides, Reward, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Substance-Related Disorders, Intracellular Signaling Peptides and Proteins, Rats
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