{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T12:00:54Z","timestamp":1778673654303,"version":"3.51.4"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA033344"],"award-info":[{"award-number":["DA033344"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA006420"],"award-info":[{"award-number":["AA006420"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA026999"],"award-info":[{"award-number":["AA026999"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>Hypothalamic orexin (Orx) projections to the paraventricular nucleus of the thalamus (PVT) have received growing interest because of their role in drug-seeking behavior. Using an established model of cocaine dependence (i.e., long access [LgA] to cocaine), we previously showed that OrxA injections in the posterior PVT (pPVT) reinstated extinguished cocaine-seeking behavior in rats after an intermediate period of abstinence (2\u20133 weeks). Considering the long-lasting nature of drug-seeking behavior, the present study examined whether the priming effect of intra-pPVT OrxA administration was preserved after a period of protracted abstinence (4\u20135 weeks) in rats that self-administered cocaine under LgA conditions. Furthermore, to better understand whether a history of cocaine dependence affects the Orx system\u2014particularly the hypothalamic Orx\u2194pPVT connection\u2014the number of Orx-expressing cells in the lateral hypothalamus (LH), dorsomedial hypothalamus (DMH), and perifornical area (PFA) and number of orexin receptor 1 (OrxR1)- and OrxR2-expressing cells in the pPVT were quantified. Orexin A administration in the pPVT induced cocaine-seeking behavior after intermediate abstinence, as reported previously. At protracted abstinence, however, the priming effect of OrxA was absent. A higher number of cells that expressed Orx was observed in the LH\/DMH\/PFA at both intermediate and protracted abstinence. In the pPVT, the number of OrxR2-expressing cells was significantly higher only at intermediate abstinence, with no changes in the number of OrxR1-expressing cells. These data build on our previous findings that the hypothalamic Orx\u2194pPVT connection is strongly recruited shortly after cocaine abstinence and demonstrate that the priming effect of OrxA is not long lasting. Furthermore, these findings suggest that throughout abstinence, the Orx\u2194pPVT connection undergoes neuroadaptive changes, reflected by alterations of the number of OrxR2-expressing cells in the pPVT.<\/jats:p>","DOI":"10.3389\/fnbeh.2021.620868","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T06:30:22Z","timestamp":1614061822000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"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"],"prefix":"10.3389","volume":"15","author":[{"given":"Alessandra","family":"Matzeu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R\u00e9mi","family":"Martin-Fardon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.brainres.2009.09.106","article-title":"Lateral hypothalamic orexin\/hypocretin neurons: a role in reward-seeking and addiction.","volume":"1314","author":"Aston-Jones","year":"2010","journal-title":"Brain Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1002\/cne.10783","article-title":"Overlapping distributions of orexin\/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress.","volume":"464","author":"Baldo","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1002\/cne.21265","article-title":"Expression of the mRNAs encoding for the vesicular glutamate transporters 1 and 2 in the rat thalamus.","volume":"501","author":"Barroso-Chinea","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1016\/j.neuron.2007.12.019","article-title":"Cocaine seeking habits depend upon dopamine-dependent serial connectivity linking the ventral with the dorsal striatum.","volume":"57","author":"Belin","year":"2008","journal-title":"Neuron"},{"key":"B5","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/s0079-6123(08)63047-2","article-title":"The specificity of the nonspecific thalamus: the midline nuclei.","volume":"87","author":"Bentivoglio","year":"1991","journal-title":"Prog. Brain Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/s0306-4522(97)00577-0","article-title":"Neuroanatomical basis for facilitation of hypothalamic-pituitary-adrenal responses to a novel stressor after chronic stress.","volume":"84","author":"Bhatnagar","year":"1998","journal-title":"Neuroscience"},{"key":"B7","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/(sici)1098-2396(199904)32:1<13::aid-syn2>3.0.co;2-r","article-title":"Stress induces fos expression in neurons of the thalamic paraventricular nucleus that innervate limbic forebrain sites.","volume":"32","author":"Bubser","year":"1999","journal-title":"Synapse"},{"key":"B8","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neuroscience.2010.02.002","article-title":"The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats.","volume":"167","author":"Choi","year":"2010","journal-title":"Neuroscience"},{"key":"B9","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.neuroscience.2012.02.036","article-title":"Orexin signaling in the paraventricular thalamic nucleus modulates mesolimbic dopamine and hedonic feeding in the rat.","volume":"210","author":"Choi","year":"2012","journal-title":"Neuroscience"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.neubiorev.2014.11.021","article-title":"Limbic thalamus and state-dependent behavior: the paraventricular nucleus of the thalamic midline as a node in circadian timing and sleep\/wake-regulatory networks.","volume":"54","author":"Colavito","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/s0006-3223(98)00288-1","article-title":"Are different parts of the extended amygdala involved in fear versus anxiety?","volume":"44","author":"Davis","year":"1998","journal-title":"Biol. Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/npp.2009.109","article-title":"Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety.","volume":"35","author":"Davis","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"B13","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.biopsych.2007.02.002","article-title":"Stimuli linked to ethanol availability activate hypothalamic CART and orexin neurons in a reinstatement model of relapse.","volume":"63","author":"Dayas","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"B14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/b978-0-444-59489-1.00003-3","article-title":"Hypocretins and the neurobiology of sleep-wake mechanisms.","volume":"198","author":"de Lecea","year":"2012","journal-title":"Prog. Brain Res."},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/s0165-0173(01)00088-1","article-title":"The neuropsychological basis of addictive behaviour.","volume":"36","author":"Everitt","year":"2001","journal-title":"Brain Res. Brain Res. Rev."},{"key":"B17","doi-asserted-by":"publisher","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.","author":"Fragale","year":"2020","journal-title":"Addict. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/0166-2236(94)90074-4","article-title":"The specificity of the \u2018nonspecific\u2019 midline and intralaminar thalamic nuclei.","volume":"17","author":"Groenewegen","year":"1994","journal-title":"Trends Neurosci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1111\/acer.13826","article-title":"Pituitary adenylate cyclase-activating polypeptide-27 (PACAP-27) in the thalamic paraventricular nucleus is stimulated by ethanol drinking.","volume":"42","author":"Gupta","year":"2018","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/nature04071","article-title":"A role for lateral hypothalamic orexin neurons in reward seeking.","volume":"437","author":"Harris","year":"2005","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1124\/jpet.103.052092","article-title":"Corticotropin-releasing factor in brain: a role in activation, arousal, and affect regulation.","volume":"311","author":"Heinrichs","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1002\/cne.21934","article-title":"Paraventricular thalamic nucleus: subcortical connections and innervation by serotonin, orexin, and corticotropin-releasing hormone in macaque monkeys.","volume":"512","author":"Hsu","year":"2009","journal-title":"J. Comp. Neurol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1152\/jn.00927.2005","article-title":"Prefrontal cortex-projecting glutamatergic thalamic paraventricular nucleus-excited by hypocretin: a feedforward circuit that may enhance cognitive arousal.","volume":"95","author":"Huang","year":"2006","journal-title":"J. Neurophysiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/cne.20444","article-title":"Vglut2 afferents to the medial prefrontal and primary somatosensory cortices: a combined retrograde tracing in situ hybridization study [corrected].","volume":"483","author":"Hur","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.peptides.2004.10.014","article-title":"Effects of orexins\/hypocretins on neuronal activity in the paraventricular nucleus of the thalamus in rats in vitro.","volume":"26","author":"Ishibashi","year":"2005","journal-title":"Peptides"},{"key":"B27","doi-asserted-by":"publisher","first-page":"6247","DOI":"10.1523\/jneurosci.22-14-06247.2002","article-title":"Dopamine release in the dorsal striatum during cocaine-seeking behavior under the control of a drug-associated cue.","volume":"22","author":"Ito","year":"2002","journal-title":"J. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/7854_2016_56","article-title":"Role of the orexin\/hypocretin system in stress-related psychiatric disorders.","volume":"33","author":"James","year":"2017","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B29","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/b978-0-444-59489-1.00009-4","article-title":"Orexin, stress, and anxiety\/panic states.","volume":"198","author":"Johnson","year":"2012","journal-title":"Prog. Brain Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/nm.2075","article-title":"A key role for orexin in panic anxiety.","volume":"16","author":"Johnson","year":"2010","journal-title":"Nat. Med."},{"key":"B32","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1111\/j.1476-5381.2010.01088.x","article-title":"Discrete cue-conditioned alcohol-seeking after protracted abstinence: pattern of neural activation and involvement of orexin(1) receptors.","volume":"162","author":"Jupp","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.1176\/appi.ajp.162.8.1403","article-title":"The neural basis of addiction: a pathology of motivation and choice.","volume":"162","author":"Kalivas","year":"2005","journal-title":"Am. J. Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.neubiorev.2015.08.005","article-title":"Placing the paraventricular nucleus of the thalamus within the brain circuits that control behavior.","volume":"56","author":"Kirouac","year":"2015","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.brainres.2005.08.035","article-title":"Orexin (hypocretin) innervation of the paraventricular nucleus of the thalamus.","volume":"1059","author":"Kirouac","year":"2005","journal-title":"Brain Res."},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.3389\/fnbeh.2014.00132","article-title":"Intrinsic properties and neuropharmacology of midline paraventricular thalamic nucleus neurons.","volume":"8","author":"Kolaj","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"B37","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/npp.2009.110","article-title":"Neurocircuitry of addiction.","volume":"35","author":"Koob","year":"2010","journal-title":"Neuropsychopharmacology"},{"key":"B38","doi-asserted-by":"publisher","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":"B39","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1002\/cne.21502","article-title":"Projections from the paraventricular nucleus of the thalamus to the forebrain, with special emphasis on the extended amygdala.","volume":"506","author":"Li","year":"2008","journal-title":"J. Comp. Neurol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.pbb.2009.12.016","article-title":"Changes in emotional behavior produced by orexin microinjections in the paraventricular nucleus of the thalamus.","volume":"95","author":"Li","year":"","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B41","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00213-010-1948-y","article-title":"Orexins in the paraventricular nucleus of the thalamus mediate anxiety-like responses in rats.","volume":"212","author":"Li","year":"","journal-title":"Psychopharmacology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"14102","DOI":"10.1523\/jneurosci.4079-10.2010","article-title":"Medial dorsal hypothalamus mediates the inhibition of reward seeking after extinction.","volume":"30","author":"Marchant","year":"2010","journal-title":"J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1523\/jneurosci.5194-08.2009","article-title":"Lateral hypothalamus is required for context-induced reinstatement of extinguished reward seeking.","volume":"29","author":"Marchant","year":"2009","journal-title":"J. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s00018-011-0817-0","article-title":"The hypothalamus and the neurobiology of drug seeking.","volume":"69","author":"Marchant","year":"2012","journal-title":"Cell Mol. Life. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1002\/cne.1190","article-title":"Differential expression of orexin receptors 1 and 2 in the rat brain.","volume":"435","author":"Marcus","year":"2001","journal-title":"J. Comp. Neurol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1111\/adb.12374","article-title":"Perseveration of craving: effects of stimuli conditioned to drugs of abuse versus conventional reinforcers differing in demand.","volume":"22","author":"Martin-Fardon","year":"2017","journal-title":"Addict. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/adb.12441","article-title":"Differential role of hypothalamic orexin\/hypocretin neurons in reward seeking motivated by cocaine versus palatable food.","volume":"23","author":"Martin-Fardon","year":"2016","journal-title":"Addict. Biol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1111\/adb.12441","article-title":"Differential role of hypothalamic orexin\/hypocretin neurons in reward seeking motivated by cocaine versus palatable food.","volume":"23","author":"Martin-Fardon","year":"2018","journal-title":"Addict. Biol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.brainres.2009.12.027","article-title":"Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: focus on corticotropin-releasing factor, nociceptin\/orphanin FQ, and orexin\/hypocretin.","volume":"1314","author":"Martin-Fardon","year":"2010","journal-title":"Brain Res."},{"key":"B50","doi-asserted-by":"crossref","DOI":"10.3389\/fnint.2020.599710","article-title":"Blockade of orexin receptors in the posterior paraventricular nucleus of the thalamus prevents stress-induced reinstatement of reward-seeking behavior in rats with a history of ethanol dependence.","volume":"14","author":"Matzeu","year":"2020","journal-title":"Front. Integr. Neurosci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/adb.12280","article-title":"The paraventricular nucleus of the thalamus is differentially recruited by stimuli conditioned to the availability of cocaine versus palatable food.","volume":"22","author":"Matzeu","year":"2017","journal-title":"Addict. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1038\/npp.2017.250","article-title":"Dynorphin counteracts orexin in the paraventricular nucleus of the thalamus: cellular and behavioral evidence.","volume":"43","author":"Matzeu","year":"2018","journal-title":"Neuropsychopharmacology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1124\/jpet.116.235945","article-title":"Orexin-A\/Hypocretin-1 mediates cocaine-seeking behavior in the posterior paraventricular nucleus of the thalamus via orexin\/hypocretin receptor-2.","volume":"359","author":"Matzeu","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B54","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.neulet.2015.10.016","article-title":"Transient inactivation of the posterior paraventricular nucleus of the thalamus blocks cocaine-seeking behavior.","volume":"608","author":"Matzeu","year":"2015","journal-title":"Neurosci. Lett."},{"key":"B55","doi-asserted-by":"publisher","first-page":"8655","DOI":"10.1523\/jneurosci.21-21-08655.2001","article-title":"The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior.","volume":"21","author":"McFarland","year":"2001","journal-title":"J. Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/s0959-4388(02)00331-8","article-title":"Sleep, feeding, and neuropeptides: roles of orexins and orexin receptors.","volume":"12","author":"Mieda","year":"2002","journal-title":"Curr. Opin. Neurobiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1016\/j.bbr.2010.10.037","article-title":"Extinction of drug seeking.","volume":"217","author":"Millan","year":"2011","journal-title":"Behav. Brain Res."},{"key":"B58","first-page":"R1620","article-title":"Daily rhythms in Fos activity in the rat ventrolateral preoptic area and midline thalamic nuclei.","volume":"275","author":"Novak","year":"1998","journal-title":"Am. J. Physiol."},{"key":"B59","doi-asserted-by":"crossref","first-page":"R1267","DOI":"10.1152\/ajpregu.2000.278.5.R1267","article-title":"Rhythms in Fos expression in brain areas related to the sleep-wake cycle in the diurnal Arvicanthis niloticus.","volume":"278","author":"Novak","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/s0168-0102(02)00042-1","article-title":"Fos expression in afferents to the rat midline thalamus following immobilization stress.","volume":"43","author":"Otake","year":"2002","journal-title":"Neurosci Res."},{"key":"B61","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":"B62","author":"Paxinos","year":"1997","journal-title":"The Rat Brain in Stereotaxic Coordinates"},{"key":"B63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF00229852","article-title":"Fos-related protein expression in the midline paraventricular nucleus of the rat thalamus: basal oscillation and relationship with limbic efferents.","volume":"104","author":"Peng","year":"1995","journal-title":"Exp. Brain Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"9996","DOI":"10.1523\/jneurosci.18-23-09996.1998","article-title":"Neurons containing hypocretin (orexin) project to multiple neuronal systems.","volume":"18","author":"Peyron","year":"1998","journal-title":"J. Neurosci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1523\/jneurosci.5724-09.2010","article-title":"Hypocretins regulate the anxiogenic-like effects of nicotine and induce reinstatement of nicotine-seeking behavior.","volume":"30","author":"Plaza-Zabala","year":"2010","journal-title":"J. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/0006-8993(83)90934-4","article-title":"Two types of medial hypothalamic inhibition of lateral hypothalamic reward.","volume":"277","author":"Porrino","year":"1983","journal-title":"Brain Res."},{"key":"B67","doi-asserted-by":"publisher","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":"B68","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.tips.2011.03.007","article-title":"Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal.","volume":"32","author":"Sakurai","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1111\/j.1749-6632.2010.05513.x","article-title":"The orexin system: roles in sleep\/wake regulation.","volume":"1200","author":"Sakurai","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/s0166-4328(01)00307-2","article-title":"Cortical arousal induced by microinjection of orexins into the paraventricular nucleus of the rat.","volume":"128","author":"Sato-Suzuki","year":"2002","journal-title":"Behav. Brain Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"277","DOI":"10.2174\/157015906778520773","article-title":"Neurochemistry of the nucleus accumbens and its relevance to depression and antidepressant action in rodents.","volume":"4","author":"Shirayama","year":"2006","journal-title":"Curr. Neuropharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1124\/pr.109.001933","article-title":"Drug wanting: behavioral sensitization and relapse to drug-seeking behavior.","volume":"63","author":"Steketee","year":"2011","journal-title":"Pharmacol. Rev."},{"key":"B73","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1002\/1097-4547(20001015)62:2<161::aid-jnr1>3.0.co;2-1","article-title":"The hypocretins: excitatory neuromodulatory peptides for multiple homeostatic systems, including sleep and feeding.","volume":"62","author":"Sutcliffe","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"B74","doi-asserted-by":"publisher","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":"B75","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/s0014-5793(98)01266-6","article-title":"Distribution of orexin receptor mRNA in the rat brain.","volume":"438","author":"Trivedi","year":"1998","journal-title":"FEBS Lett."},{"key":"B76","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/s0165-0173(02)00181-9","article-title":"The intralaminar and midline nuclei of the thalamus. anatomical and functional evidence for participation in processes of arousal and awareness.","volume":"39","author":"Van der Werf","year":"2002","journal-title":"Brain Res. Brain Res. Rev."},{"key":"B77","doi-asserted-by":"publisher","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":"B78","doi-asserted-by":"publisher","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. Physiol."},{"key":"B79","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1471-4159.2007.04748.x","article-title":"Long-lasting up-regulation of orexin receptor type 2 protein levels in the rat nucleus accumbens after chronic cocaine administration.","volume":"103","author":"Zhang","year":"2007","journal-title":"J. Neurochem."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1016\/j.neuroscience.2008.03.023","article-title":"Effects of cocaine place conditioning, chronic escalating-dose \u201cbinge\u201d pattern cocaine administration and acute withdrawal on orexin\/hypocretin and preprodynorphin gene expressions in lateral hypothalamus of fischer and sprague-dawley rats.","volume":"153","author":"Zhou","year":"2008","journal-title":"Neuroscience"}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2021.620868\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T19:42:07Z","timestamp":1697917327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2021.620868\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,23]]},"references-count":80,"alternative-id":["10.3389\/fnbeh.2021.620868"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2021.620868","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,23]]},"article-number":"620868"}}