{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T21:10:08Z","timestamp":1794345008606,"version":"4.9.0"},"reference-count":104,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"am","delay-in-days":334,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R00 DA045675"],"award-info":[{"award-number":["R00 DA045675"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DA006214"],"award-info":[{"award-number":["R01 DA006214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["biologicalpsychiatryjournal.com","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biological Psychiatry"],"published-print":{"date-parts":[[2022,12]]},"DOI":"10.1016\/j.biopsych.2022.06.027","type":"journal-article","created":{"date-parts":[[2022,7,3]],"date-time":"2022-07-03T19:20:02Z","timestamp":1656876002000},"page":"836-844","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":55,"title":["Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction"],"prefix":"10.1016","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-8607","authenticated-orcid":false,"given":"Morgan H.","family":"James","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Aston-Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biopsych.2022.06.027_bib1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/79690","article-title":"A\u00a0mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains","volume":"6","author":"Peyron","year":"2000","journal-title":"Nat Med"},{"key":"10.1016\/j.biopsych.2022.06.027_bib2","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1073\/pnas.95.1.322","article-title":"The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity","volume":"95","author":"de Lecea","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2022.06.027_bib3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0092-8674(00)80949-6","article-title":"Orexins and orexin receptors: A family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior","volume":"92","author":"Sakurai","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.biopsych.2022.06.027_bib4","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0092-8674(00)81973-X","article-title":"Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation","volume":"98","author":"Chemelli","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.biopsych.2022.06.027_bib5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S0092-8674(00)81965-0","article-title":"The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene","volume":"98","author":"Lin","year":"1999","journal-title":"Cell"},{"key":"10.1016\/j.biopsych.2022.06.027_bib6","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nature04071","article-title":"A\u00a0role for lateral hypothalamic orexin neurons in reward seeking","volume":"437","author":"Harris","year":"2005","journal-title":"Nature"},{"key":"10.1016\/j.biopsych.2022.06.027_bib7","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/nn.3810","article-title":"Motivational activation: A unifying hypothesis of orexin\/hypocretin function","volume":"17","author":"Mahler","year":"2014","journal-title":"Nat Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib8","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1523\/JNEUROSCI.23-08-03106.2003","article-title":"Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal","volume":"23","author":"Georgescu","year":"2003","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.biopsych.2008.03.006","article-title":"Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell","volume":"64","author":"Sharf","year":"2008","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib10","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.biopsych.2018.07.022","article-title":"Increased number and activity of a lateral subpopulation of hypothalamic orexin\/hypocretin neurons underlies the expression of an addicted state in rats","volume":"85","author":"James","year":"2019","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2021.620868","article-title":"Cocaine-seeking behavior induced by orexin A administration in the posterior paraventricular nucleus of the thalamus is not long-lasting: Neuroadaptation of the orexin system during cocaine abstinence","volume":"15","author":"Matzeu","year":"2021","journal-title":"Front Behav Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib12","doi-asserted-by":"crossref","DOI":"10.1111\/adb.12946","article-title":"Intermittent self-administration of fentanyl induces a multifaceted addiction state associated with persistent changes in the orexin system","volume":"26","author":"Fragale","year":"2021","journal-title":"Addict Biol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib13","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aao4953","article-title":"Opiates increase the number of hypocretin-producing cells in human and mouse brain and reverse cataplexy in a mouse model of narcolepsy","volume":"10","author":"Thannickal","year":"2018","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.biopsych.2022.06.027_bib14","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1111\/acer.14126","article-title":"Embryonic ethanol exposure affects the early development, migration, and location of hypocretin\/orexin neurons in zebrafish","volume":"43","author":"Collier","year":"2019","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.pnpbp.2019.109728","article-title":"Maternal ethanol consumption before paternal fertilization: Stimulation of hypocretin neurogenesis and ethanol intake in zebrafish offspring","volume":"96","author":"Collier","year":"2020","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib16","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-95707-y","article-title":"Sexually dimorphic and asymmetric effects of embryonic ethanol exposure on hypocretin\/orexin neurons as related to behavioral changes in zebrafish","volume":"11","author":"Collier","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.biopsych.2022.06.027_bib17","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/BF00439560","article-title":"Self-administration of cocaine on a progressive ratio schedule in rats: Dose\u2013response relationship and effect of haloperidol pretreatment","volume":"97","author":"Roberts","year":"1989","journal-title":"Psychopharmacol (Berl)"},{"key":"10.1016\/j.biopsych.2022.06.027_bib18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00213-012-2899-2","article-title":"The behavioral economics of drug self-administration: A review and new analytical approach for within-session procedures","volume":"226","author":"Bentzley","year":"2013","journal-title":"Psychopharmacol (Berl)"},{"key":"10.1016\/j.biopsych.2022.06.027_bib19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1037\/0033-295X.115.1.186","article-title":"Economic demand and essential value","volume":"115","author":"Hursh","year":"2008","journal-title":"Psychol Rev"},{"key":"10.1016\/j.biopsych.2022.06.027_bib20","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/npp.2008.195","article-title":"Behavioral economic assessment of price and cocaine consumption following self-administration histories that produce escalation of either final ratios or intake","volume":"34","author":"Oleson","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib21","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1038\/npp.2012.37","article-title":"The motivation to self-administer is increased after a history of spiking brain levels of cocaine","volume":"37","author":"Zimmer","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib22","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1523\/JNEUROSCI.2604-17.2017","article-title":"Amphetamine reverses escalated cocaine intake via restoration of dopamine transporter conformation","volume":"38","author":"Siciliano","year":"2018","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib23","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/npp.2014.238","article-title":"Brief intermittent cocaine self-administration and abstinence sensitizes cocaine effects on the dopamine transporter and increases drug seeking","volume":"40","author":"Calipari","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib24","doi-asserted-by":"crossref","first-page":"11822","DOI":"10.1073\/pnas.1406324111","article-title":"Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat","volume":"111","author":"Bentzley","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2022.06.027_bib25","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.biopsych.2016.11.011","article-title":"Oxytocin acts in nucleus accumbens to attenuate methamphetamine seeking and demand","volume":"81","author":"Cox","year":"2017","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib26","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/ijnp\/pyaa040","article-title":"Sex differences in demand for highly palatable foods: Role of the orexin system","volume":"24","author":"Freeman","year":"2021","journal-title":"Int J Neuropsychopharmacol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib27","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1523\/JNEUROSCI.21-05-01656.2001","article-title":"Fos expression in orexin neurons varies with behavioral state","volume":"21","author":"Estabrooke","year":"2001","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib28","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.neuron.2005.04.035","article-title":"Behavioral correlates of activity in identified hypocretin\/orexin neurons","volume":"46","author":"BY","year":"2005","journal-title":"Neuron"},{"key":"10.1016\/j.biopsych.2022.06.027_bib29","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1111\/j.1460-9568.2009.06952.x","article-title":"Hypocretin\/orexin contributes to the expression of some but not all forms of stress and arousal","volume":"30","author":"Furlong","year":"2009","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib30","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.tins.2006.08.002","article-title":"Arousal and reward: A dichotomy in orexin function","volume":"29","author":"Harris","year":"2006","journal-title":"Trends Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib31","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neuropharm.2018.09.033","article-title":"Activation of lateral hypothalamic group III metabotropic glutamate receptors suppresses cocaine-seeking following abstinence and normalizes drug-associated increases in excitatory drive to orexin\/hypocretin cells","volume":"154","author":"Yeoh","year":"2019","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib32","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0167-0115(01)00340-8","article-title":"Effects of restricted feeding on the activity of hypothalamic orexin (OX)-A containing neurons and OX2 receptor mRNA level in the paraventricular nucleus of rats","volume":"104","author":"Kurose","year":"2002","journal-title":"Regul Pept"},{"key":"10.1016\/j.biopsych.2022.06.027_bib33","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/j.physbeh.2012.04.016","article-title":"Orexin 1 receptors are a novel target to modulate panic responses and the panic brain network","volume":"107","author":"Johnson","year":"2012","journal-title":"Physiol Behav"},{"key":"10.1016\/j.biopsych.2022.06.027_bib34","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1111\/ejn.13170","article-title":"Orexin\/hypocretin neuron activation is correlated with alcohol seeking and preference in a topographically specific manner","volume":"43","author":"Moorman","year":"2016","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib35","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0178573","article-title":"Diurnal fluctuation in the number of hypocretin\/orexin and histamine producing: Implication for understanding and treating neuronal loss","volume":"12","author":"McGregor","year":"2017","journal-title":"PLOS ONE"},{"key":"10.1016\/j.biopsych.2022.06.027_bib36","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0110385","article-title":"Effects of vivo morpholino knockdown of lateral hypothalamus orexin\/hypocretin on renewal of alcohol seeking","volume":"9","author":"Prasad","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.biopsych.2022.06.027_bib37","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/sj.bjp.0706789","article-title":"The orexin system regulates alcohol-seeking in rats","volume":"148","author":"Lawrence","year":"2006","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib38","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1111\/acer.14296","article-title":"Moderate prenatal ethanol exposure stimulates CXCL12\/CXCR4 chemokine system in radial glia progenitor cells in hypothalamic neuroepithelium and peptide neurons in lateral hypothalamus of the embryo and postnatal offspring","volume":"44","author":"Chang","year":"2020","journal-title":"Alcohol Clin Exp Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib39","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1210\/en.2014-1961","article-title":"A\u00a0stereological analysis of NPY, POMC, orexin, GFAP astrocyte, and Iba1 microglia cell number and volume in diet-induced obese male mice","volume":"156","author":"Lemus","year":"2015","journal-title":"Endocrinology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib40","doi-asserted-by":"crossref","first-page":"R1454","DOI":"10.1152\/ajpregu.00286.2002","article-title":"Peptides that regulate food intake: Orexin gene expression is increased during states of hypertriglyceridemia","volume":"284","author":"Wortley","year":"2003","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib41","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.pbb.2010.06.013","article-title":"Increased orexin and melanin-concentrating hormone expression in the perifornical lateral hypothalamus of rats prone to overconsuming a fat-rich diet","volume":"96","author":"Morganstern","year":"2010","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1016\/j.biopsych.2022.06.027_bib42","doi-asserted-by":"crossref","first-page":"11215","DOI":"10.1523\/JNEUROSCI.6096-08.2009","article-title":"Orexin A\/hypocretin-1 selectively promotes motivation for positive reinforcers","volume":"29","author":"Borgland","year":"2009","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib43","doi-asserted-by":"crossref","first-page":"6742","DOI":"10.1523\/JNEUROSCI.22-15-06742.2002","article-title":"Differential activation of orexin neurons by antipsychotic drugs associated with weight gain","volume":"22","author":"Fadel","year":"2002","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib44","doi-asserted-by":"crossref","DOI":"10.1111\/adb.12795","article-title":"The number of lateral hypothalamus orexin\/hypocretin neurons contributes to individual differences in cocaine demand","volume":"25","author":"Pantazis","year":"2020","journal-title":"Addict Biol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib45","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1111\/ejn.14166","article-title":"Demand elasticity predicts addiction endophenotypes and the therapeutic efficacy of an orexin\/hypocretin-1 receptor antagonist in rats","volume":"50","author":"James","year":"2019","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib46","article-title":"The dual orexin\/hypocretin receptor antagonist suvorexant reduces addiction-like behaviors for the opioid fentanyl","author":"O\u2019Connor","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.biopsych.2022.06.027_bib47","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/npp.2014.293","article-title":"Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats","volume":"40","author":"Schmeichel","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib48","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.brainres.2016.10.018","article-title":"Orexin\/hypocretin-1 receptor antagonism reduces ethanol self-administration and reinstatement selectively in highly-motivated rats","volume":"1654","author":"Moorman","year":"2017","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib49","doi-asserted-by":"crossref","first-page":"9831","DOI":"10.1523\/JNEUROSCI.0255-19.2019","article-title":"Orexin-1 receptor signaling in ventral pallidum regulates motivation for the opioid remifentanil","volume":"39","author":"Mohammadkhani","year":"2019","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib50","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2019.04.017","article-title":"The orexin-1 receptor antagonist SB-334867 reduces motivation, but not inhibitory control, in a rat stop signal task","volume":"1731","author":"Wiskerke","year":"2020","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib51","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1177\/0269881115615107","article-title":"Effects of lisdexamfetamine in a rat model of binge-eating","volume":"29","author":"Vickers","year":"2015","journal-title":"J\u00a0Psychopharmacol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib52","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.bbr.2014.06.049","article-title":"Binge-like consumption of caloric and non-caloric palatable substances in ad libitum-fed C57BL\/6J mice: Pharmacological and molecular evidence of orexin involvement","volume":"272","author":"Alcaraz-Iborra","year":"2014","journal-title":"Behav Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib53","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0095019","article-title":"A\u00a0relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior","volume":"9","author":"Rorabaugh","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.biopsych.2022.06.027_bib54","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1038\/s41386-021-01052-z","article-title":"Sleep dysregulation in binge eating disorder and \u201cfood addiction\u201d: The orexin (hypocretin) system as a potential neurobiological link","volume":"46","author":"Mehr","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.brainres.2011.03.045","article-title":"The orexin1 receptor antagonist SB-334867 dissociates the motivational properties of alcohol and sucrose in rats","volume":"1391","author":"Jupp","year":"2011","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib56","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.pnpbp.2017.06.028","article-title":"Palatable food self-administration and reinstatement are not affected by dual orexin receptor antagonism","volume":"87","author":"Khoo","year":"2018","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib57","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2020.146665","article-title":"Introduction to the Special Issue: \u201cMaking orexin-based therapies for addiction a reality: What are the steps from here?\u201d","volume":"1731","author":"James","year":"2020","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib58","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41386-020-0619-x","article-title":"Repurposing the dual orexin receptor antagonist suvorexant for the treatment of opioid use disorder: Why sleep on this any longer?","volume":"45","author":"James","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib59","doi-asserted-by":"crossref","DOI":"10.1038\/srep16143","article-title":"Orexin\/Hypocretin-1 receptor antagonism selectively reduces cue-induced feeding in sated rats and recruits medial prefrontal cortex and thalamus","volume":"5","author":"Cole","year":"2015","journal-title":"Sci Rep"},{"key":"10.1016\/j.biopsych.2022.06.027_bib60","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/npp.2017.158","article-title":"Effects of suvorexant, a dual orexin\/hypocretin receptor antagonist, on impulsive behavior associated with cocaine","volume":"43","author":"Gentile","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib61","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41386-018-0292-5","article-title":"NIDA\u2019s medication development priorities in response to the Opioid Crisis: Ten most wanted","volume":"44","author":"Rasmussen","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib62","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2018.08.005","article-title":"A\u00a0sleeping giant: Suvorexant for the treatment of alcohol use disorder?","volume":"1731","author":"Campbell","year":"2020","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2019.146597","article-title":"Suvorexant to treat alcohol use disorder and comorbid insomnia: Plan for a phase II trial","volume":"1728","author":"Campbell","year":"2020","journal-title":"Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib64","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3390\/brainsci10040226","article-title":"Targeting the orexin system for prescription opioid use disorder","volume":"10","author":"Matzeu","year":"2020","journal-title":"Brain Sci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib65","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000514965","article-title":"The insomnia-addiction positive feedback loop: Role of the orexin system","volume":"45","author":"Fragale","year":"2021","journal-title":"Front Neurol Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib66","first-page":"704","article-title":"Pharmacotherapy in narcolepsy","volume":"21","author":"Akimoto","year":"1960","journal-title":"Dis Nerv Syst"},{"key":"10.1016\/j.biopsych.2022.06.027_bib67","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0301-0082(96)00070-6","article-title":"Pharmacological aspects of human and canine narcolepsy","volume":"52","author":"Nishino","year":"1997","journal-title":"Prog Neurobiol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib68","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1523\/JNEUROSCI.2458-17.2017","article-title":"Are cocaine-seeking \u201chabits\u201d necessary for the development of addiction-like behavior in rats?","volume":"38","author":"Singer","year":"2018","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib69","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1210\/endo.141.10.7707","article-title":"Nicotine up-regulates expression of orexin and its receptors in rat brain","volume":"141","author":"Kane","year":"2000","journal-title":"Endocrinology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pbb.2014.01.013","article-title":"Blocking of corticotrophin releasing factor receptor-1 during footshock attenuates context fear but not the upregulation of prepro-orexin mRNA in rats","volume":"120","author":"Chen","year":"2014","journal-title":"Pharmacol Biochem Behav"},{"key":"10.1016\/j.biopsych.2022.06.027_bib71","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1007\/s00429-013-0626-3","article-title":"Orexins (hypocretins) contribute to fear and avoidance in rats exposed to a single episode of footshocks","volume":"219","author":"Chen","year":"2014","journal-title":"Brain Struct Funct"},{"key":"10.1016\/j.biopsych.2022.06.027_bib72","doi-asserted-by":"crossref","first-page":"RC168","DOI":"10.1523\/JNEUROSCI.21-19-j0003.2001","article-title":"Orexin (hypocretin) neurons contain dynorphin","volume":"21","author":"Chou","year":"2001","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib73","doi-asserted-by":"crossref","first-page":"13037","DOI":"10.1523\/JNEUROSCI.3380-06.2006","article-title":"Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin\/orexin neuropeptides","volume":"26","author":"Li","year":"2006","journal-title":"J\u00a0Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib74","doi-asserted-by":"crossref","first-page":"E1648","DOI":"10.1073\/pnas.1315542111","article-title":"Hypocretin (orexin) facilitates reward by attenuating the antireward effects of its cotransmitter dynorphin in ventral tegmental area","volume":"111","author":"Muschamp","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.biopsych.2022.06.027_bib75","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.celrep.2017.01.030","article-title":"Projection-target-defined effects of orexin and dynorphin on VTA dopamine neurons","volume":"18","author":"Baimel","year":"2017","journal-title":"Cell Rep"},{"key":"10.1016\/j.biopsych.2022.06.027_bib76","doi-asserted-by":"crossref","first-page":"720","DOI":"10.3389\/fneur.2018.00720","article-title":"Drug seeking and relapse: New evidence of a role for orexin and dynorphin co-transmission in the paraventricular nucleus of the thalamus","volume":"9","author":"Matzeu","year":"2018","journal-title":"Front Neurol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib77","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0169-328X(93)90133-A","article-title":"\u2018Binge\u2019 cocaine administration induces a sustained increase of prodynorphin mRNA in rat caudate-putamen","volume":"19","author":"Spangler","year":"1993","journal-title":"Brain Res Mol Brain Res"},{"key":"10.1016\/j.biopsych.2022.06.027_bib78","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1038\/s41386-018-0054-4","article-title":"Knockdown of hypocretin attenuates extended access of cocaine self-administration in rats","volume":"43","author":"Schmeichel","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib79","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/s41386-021-01173-5","article-title":"Orexin-1 receptor signaling in ventral tegmental area mediates cue-driven demand for cocaine","volume":"47","author":"Pantazis","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib80","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.biopsych.2009.01.018","article-title":"Reinstatement of cocaine seeking by hypocretin (orexin) in the ventral tegmental area: Independence from the local corticotropin-releasing factor network","volume":"65","author":"Wang","year":"2009","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib81","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00213-012-2681-5","article-title":"Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats","volume":"226","author":"Mahler","year":"2013","journal-title":"Psychopharmacol (Berl)"},{"key":"10.1016\/j.biopsych.2022.06.027_bib82","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1017\/S1461145711000423","article-title":"Orexin-1 receptor signalling within the ventral tegmental area, but not the paraventricular thalamus, is critical to regulating cue-induced reinstatement of cocaine-seeking","volume":"14","author":"James","year":"2011","journal-title":"Int J Neuropsychopharmacol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib83","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1111\/j.1460-9568.2008.06397.x","article-title":"Orexin B\/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons","volume":"28","author":"Borgland","year":"2008","journal-title":"Eur J Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib84","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.neuron.2006.01.016","article-title":"Orexin A in the VTA is critical for the induction of synaptic plasticity and behavioral sensitization to cocaine","volume":"49","author":"Borgland","year":"2006","journal-title":"Neuron"},{"key":"10.1016\/j.biopsych.2022.06.027_bib85","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.tins.2021.09.002","article-title":"Orexin (hypocretin) and addiction","volume":"44","author":"Mehr","year":"2021","journal-title":"Trends Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib86","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3389\/fnins.2019.00088","article-title":"Nucleus accumbens shell Orexin-1 receptors are critical mediators of binge intake in excessive-drinking individuals","volume":"13","author":"Lei","year":"2019","journal-title":"Front Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib87","doi-asserted-by":"crossref","first-page":"400","DOI":"10.3389\/fnins.2016.00400","article-title":"Nucleus accumbens shell and mPFC but not insula Orexin-1 receptors promote excessive alcohol drinking","volume":"10","author":"Lei","year":"2016","journal-title":"Front Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib88","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2020.108359","article-title":"The orexin (hypocretin) neuropeptide system is a target for novel therapeutics to treat cocaine use disorder with alcohol coabuse","volume":"183","author":"James","year":"2021","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib89","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.2174\/1381612826666200316153317","article-title":"Binge eating and binge drinking: A two-way road? An integrative review","volume":"26","author":"Escriv\u00e1-Mart\u00ednez","year":"2020","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.biopsych.2022.06.027_bib90","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.biopsych.2016.10.013","article-title":"Orexins mediate sex differences in the stress response and in cognitive flexibility","volume":"81","author":"Grafe","year":"2017","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib91","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.nbd.2015.04.004","article-title":"Antidepressant effects of exercise are produced via suppression of hypocretin\/orexin and melanin-concentrating hormone in the basolateral amygdala","volume":"79","author":"Kim","year":"2015","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.biopsych.2022.06.027_bib92","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.biopsych.2021.12.019","article-title":"Orexin 1 receptor antagonism in the basolateral amygdala shifts the balance from pro- to antistress signaling and behavior","volume":"91","author":"Yaeger","year":"2022","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib93","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.biopsych.2022.02.957","article-title":"Orexin (hypocretin) signaling in the basolateral amygdala contributes to individual differences in stress sensitivity","volume":"91","author":"Gyawali","year":"2022","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.biopsych.2022.06.027_bib94","article-title":"Sleep disturbance in substance use disorders: The orexin (hypocretin) system as an emerging pharmacological target [published online ahead of print]","author":"Gyawali","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.biopsych.2022.06.027_bib95","series-title":"Vitamins & Hormones","first-page":"75","article-title":"Chapter Five: Transcriptional regulation of the hypocretin\/orexin gene","author":"Tanaka","year":"2012"},{"key":"10.1016\/j.biopsych.2022.06.027_bib96","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/nature08589","article-title":"Regulation of adaptive behaviour during fasting by hypothalamic Foxa2","volume":"462","author":"Silva","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.biopsych.2022.06.027_bib97","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.bbrc.2010.11.001","article-title":"Transcriptional regulation of the hypocretin\/orexin gene by NR6A1","volume":"403","author":"Tanaka","year":"2010","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.biopsych.2022.06.027_bib98","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0004254","article-title":"IGFBP3 colocalizes with and regulates hypocretin (orexin)","volume":"4","author":"Honda","year":"2009","journal-title":"PLoS One"},{"key":"10.1016\/j.biopsych.2022.06.027_bib99","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neuron.2019.01.016","article-title":"The molecular basis of drug addiction: Linking epigenetic to synaptic and circuit mechanisms","volume":"102","author":"Nestler","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.biopsych.2022.06.027_bib100","doi-asserted-by":"crossref","first-page":"379","DOI":"10.31887\/DCNS.2019.21.4\/pkenny","article-title":"Transcriptional mechanisms of drug addiction","volume":"21","author":"Bali","year":"2019","journal-title":"Dialogues Clin Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib101","doi-asserted-by":"crossref","first-page":"335","DOI":"10.31887\/DCNS.2014.16.3\/pkenny","article-title":"Epigenetics, microRNA, and addiction","volume":"16","author":"Kenny","year":"2014","journal-title":"Dialogues Clin Neurosci"},{"key":"10.1016\/j.biopsych.2022.06.027_bib102","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1113\/jphysiol.2012.246983","article-title":"Repeated in\u00a0vivo exposure of cocaine induces long-lasting synaptic plasticity in hypocretin\/orexin-producing neurons in the lateral hypothalamus in mice","volume":"591","author":"Rao","year":"2013","journal-title":"J\u00a0Physiol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib103","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1113\/jphysiol.2012.230268","article-title":"Cocaine potentiates excitatory drive in the perifornical\/lateral hypothalamus","volume":"590","author":"Yeoh","year":"2012","journal-title":"J\u00a0Physiol"},{"key":"10.1016\/j.biopsych.2022.06.027_bib104","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1530\/eje.0.1500737","article-title":"Orexin A and B levels in the hypothalamus of female rats: The effects of the estrous cycle and age","volume":"150","author":"Porkka-Heiskanen","year":"2004","journal-title":"Eur J Endocrinol"}],"container-title":["Biological Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000632232201397X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S000632232201397X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T15:16:13Z","timestamp":1757776573000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S000632232201397X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":104,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["S000632232201397X"],"URL":"https:\/\/doi.org\/10.1016\/j.biopsych.2022.06.027","relation":{},"ISSN":["0006-3223"],"issn-type":[{"value":"0006-3223","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Orexin Reserve: A Mechanistic Framework for the Role of Orexins (Hypocretins) in Addiction","name":"articletitle","label":"Article Title"},{"value":"Biological Psychiatry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopsych.2022.06.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Society of Biological Psychiatry.","name":"copyright","label":"Copyright"}]}}