{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:55:43Z","timestamp":1778302543143,"version":"3.51.4"},"reference-count":82,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY029227"],"award-info":[{"award-number":["EY029227"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Opioid drugs are the most effective tools for treating moderate to severe pain. Despite their analgesic efficacy, long-term opioid use can lead to drug tolerance, addiction, and sleep\/wake disturbances. While the link between opioids and sleep\/wake problems is well-documented, the mechanism underlying opioid-related sleep\/wake problems remains largely unresolved. Importantly, intrinsically photosensitive retinal ganglion cells (ipRGCs), the cells that transmit environmental light\/dark information to the brain\u2019s sleep\/circadian centers to regulate sleep\/wake behavior, express \u03bc-opioid receptors (MORs). In this study, we explored the potential contribution of ipRGCs to opioid-related sleep\/circadian disruptions. Using implanted telemetry transmitters, we measured changes in horizontal locomotor activity and body temperature in mice over the course of a chronic morphine paradigm. Mice lacking MORs expressed by ipRGCs (McKO) exhibited reduced morphine-induced behavioral activation\/sensitization compared with control littermates with normal patterns of MOR expression. Contrastingly, mice lacking MORs globally (MKO) did not acquire morphine-induced locomotor activation\/sensitization. Control mice also showed morphine-induced hypothermia in both the light and dark phases, while McKO littermates only exhibited morphine-induced hypothermia in the dark. Interestingly, only control animals appeared to acquire tolerance to morphine\u2019s hypothermic effect. Morphine, however, did not acutely decrease the body temperature of MKO mice. These findings support the idea that MORs expressed by ipRGCs could contribute to opioid-related sleep\/wake problems and thermoregulatory changes.<\/jats:p>","DOI":"10.3390\/ijms232415870","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T02:54:21Z","timestamp":1670986461000},"page":"15870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["\u00b5-Opioid Receptors Expressed by Intrinsically Photosensitive Retinal Ganglion Cells Contribute to Morphine-Induced Behavioral Sensitization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2474-4912","authenticated-orcid":false,"given":"Nikolas","family":"Bergum","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-8929","authenticated-orcid":false,"given":"Casey-Tyler","family":"Berezin","sequence":"additional","affiliation":[{"name":"Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Connie M.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9862-5049","authenticated-orcid":false,"given":"Jozsef","family":"Vigh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"},{"name":"Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1001\/jamapsychiatry.2018.3126","article-title":"Prevention and Treatment of Opioid Misuse and Addiction: A Review","volume":"76","author":"Volkow","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/02791072.2020.1751900","article-title":"Sleeping Patterns in Patients with Opioid Use Disorder: Effects of Opioid Maintenance Treatment and Detoxification","volume":"52","author":"Chrobok","year":"2020","journal-title":"J. Psychoact. Drugs"},{"key":"ref_3","first-page":"4","article-title":"The Effect of Opioids on Sleep Architecture","volume":"3","author":"Dimsdale","year":"2007","journal-title":"J. Clin. Sleep Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.sleh.2017.07.007","article-title":"The Association between Insomnia and Prescription Opioid Use: Results from a Community Sample in Northeast Florida","volume":"3","author":"Serdarevic","year":"2017","journal-title":"Sleep Health"},{"key":"ref_5","first-page":"140","article-title":"Crosstalk between Sleep Disturbance and Opioid Use Disorder: A Narrative Review","volume":"12","author":"Fathi","year":"2020","journal-title":"Addict. Health"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF00420997","article-title":"Human Sleep during Chronic Morphine Intoxication","volume":"44","author":"Kay","year":"1975","journal-title":"Psychopharmacologia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1111\/pme.12910","article-title":"Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies","volume":"16","author":"Cheatle","year":"2015","journal-title":"Pain Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1016\/j.addbeh.2014.05.025","article-title":"Sleep Disturbances and Pain among Individuals with Prescription Opioid Dependence","volume":"39","author":"Hartwell","year":"2014","journal-title":"Addict. Behav."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1001\/jamapsychiatry.2018.3537","article-title":"Anxiety, Depression, and Insomnia Among Adults With Opioid Dependence Treated With Extended-Release Naltrexone vs Buprenorphine-Naloxone: A Randomized Clinical Trial and Follow-up Study","volume":"76","author":"Latif","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"ref_10","unstructured":"Huhn, A.S., and Finan, P.H. (2021). Sleep Disturbance as a Therapeutic Target to Improve Opioid Use Disorder Treatment. Exp. Clin. Psychopharmacol., Online ahead of print."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"561564","DOI":"10.3389\/fpsyt.2020.561564","article-title":"Insomnia Is Associated With Frequency of Suicidal Ideation Independent of Depression: A Replication and Extension of Findings From the National Health and Nutrition Examination Survey","volume":"11","author":"Simmons","year":"2020","journal-title":"Front. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1124\/mol.119.119107","article-title":"Bidirectional Relationship between Opioids and Disrupted Sleep: Putative Mechanisms","volume":"98","author":"Eacret","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bbr.2009.07.002","article-title":"Fentanyl, but Not Haloperidol, Entrains Persisting Circadian Activity Episodes When Administered at 24- and 31-h Intervals","volume":"205","author":"Gillman","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.pbb.2012.02.015","article-title":"Morphine Administration and Abrupt Cessation Alter the Behavioral Diurnal Activity Pattern","volume":"101","author":"Glaser","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0006-8993(00)02317-9","article-title":"Fentanyl, a Mu-Opioid Receptor Agonist, Phase Shifts the Hamster Circadian Pacemaker","volume":"868","author":"Meijer","year":"2000","journal-title":"Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1111\/j.1460-9568.2005.04131.x","article-title":"The Opioid Fentanyl Affects Light Input, Electrical Activity and Per Gene Expression in the Hamster Suprachiasmatic Nuclei","volume":"21","author":"Vansteensel","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"981939","DOI":"10.3389\/fnins.2022.981939","article-title":"A Retinal Contribution to Opioid-Induced Sleep Disorders?","volume":"16","author":"Bergum","year":"2022","journal-title":"Front. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.brainres.2008.09.043","article-title":"Opioidergic Projections to Sleep-Active Neurons in the Ventrolateral Preoptic Nucleus","volume":"1245","author":"Greco","year":"2008","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.neuron.2010.11.032","article-title":"Sleep State Switching","volume":"68","author":"Saper","year":"2010","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/npp.2012.244","article-title":"Morphine Inhibits Sleep-Promoting Neurons in the Ventrolateral Preoptic Area Via Mu Receptors and Induces Wakefulness in Rats","volume":"38","author":"Wang","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/nn.2179","article-title":"The Acute Light-Induction of Sleep Is Mediated by OPN4-Based Photoreception","volume":"11","author":"Lupi","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.neuroscience.2019.04.005","article-title":"\u03bc-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells","volume":"408","author":"Cleymaet","year":"2019","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nrn3743","article-title":"Light as a Central Modulator of Circadian Rhythms, Sleep and Affect","volume":"15","author":"LeGates","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100078","DOI":"10.1016\/j.nbscr.2022.100078","article-title":"Endogenous Opioid Signaling in the Retina Modulates Sleep\/Wake Activity in Mice","volume":"13","author":"Berezin","year":"2022","journal-title":"Neurobiol. Sleep Circadian Rhythm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1093\/jat\/28.4.260","article-title":"Postmortem Distribution of Heroin Metabolites in Femoral Blood, Liver, Cerebrospinal Fluid, and Vitreous Humor","volume":"28","author":"Wyman","year":"2004","journal-title":"J. Anal. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bergum, N., Berezin, C.-T., Dooley, G., and Vigh, J. (2022). Morphine Accumulates in the Retina Following Chronic Systemic Administration. Pharmaceuticals, 15.","DOI":"10.3390\/ph15050527"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1038\/383819a0","article-title":"Loss of Morphine-Induced Analgesia, Reward Effect and Withdrawal Symptoms in Mice Lacking the Mu-Opioid-Receptor Gene","volume":"383","author":"Matthes","year":"1996","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Weibel, R., Reiss, D., Karchewski, L., Gardon, O., Matifas, A., Filliol, D., Becker, J.A.J., Wood, J.N., Kieffer, B.L., and Gaveriaux-Ruff, C. (2013). Mu Opioid Receptors on Primary Afferent Nav1.8 Neurons Contribute to Opiate-Induced Analgesia: Insight from Conditional Knockout Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074706"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"0146-20","DOI":"10.1523\/ENEURO.0146-20.2020","article-title":"\u03bc-Opioid Receptors on Distinct Neuronal Populations Mediate Different Aspects of Opioid Reward-Related Behaviors","volume":"7","author":"Severino","year":"2020","journal-title":"eNeuro"},{"key":"ref_30","first-page":"204","article-title":"Sensitization to Repeated Morphine Injection in the Rat: Possible Involvement of A10 Dopamine Neurons","volume":"241","author":"Kalivas","year":"1987","journal-title":"J. Pharm. Exp."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1084\/jem.185.8.1517","article-title":"Altered Hematopoiesis, Behavior, and Sexual Function in Mu Opioid Receptor\u2013Deficient Mice","volume":"185","author":"Tian","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/S0893-133X(00)00252-9","article-title":"Mu Opiate Receptor Gene Dose Effects on Different Morphine Actions: Evidence for Differential in Vivo Mu Receptor Reserve","volume":"25","author":"Sora","year":"2001","journal-title":"Neuropsychopharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0304-3940(03)00410-5","article-title":"Differential Effects of Morphine and Cocaine on Locomotor Activity and Sensitization in \u03bc-Opioid Receptor Knockout Mice","volume":"344","author":"Yoo","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lfs.2017.07.016","article-title":"Long-Term Morphine Delivery via Slow Release Morphine Pellets or Osmotic Pumps: Plasma Concentration, Analgesia, and Naloxone-Precipitated Withdrawal","volume":"185","author":"McLane","year":"2017","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1124\/jpet.108.150011","article-title":"The Effects of Repeated Opioid Administration on Locomotor Activity: I. Opposing Actions of \u03bc and \u03ba Receptors","volume":"330","author":"Smith","year":"2009","journal-title":"J. Pharm. Exp."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/BF00427348","article-title":"Behavioral Effects of Low and High Acute Doses of Morphine in Solitary Mice","volume":"64","author":"Hecht","year":"1979","journal-title":"Psychopharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0091-3057(87)90496-5","article-title":"Effects of Methamphetamine and Morphine on the Vertical and Horizontal Motor Activities in Mice","volume":"27","author":"Itoh","year":"1987","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF00433065","article-title":"Biphasic Effects of a Potent Enkephalin Analogue (D-Met2,ProS)-Enkephalinamide and Morphine on Locomotor Activity in Mice","volume":"71","author":"Szkeley","year":"1980","journal-title":"Psychopharmacology"},{"key":"ref_39","first-page":"822","article-title":"Effects of Opioids, Cannabinoids, and Vanilloids on Body Temperature","volume":"S3","author":"Rawls","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nature13307","article-title":"Galanin Neurons in the Medial Preoptic Area Govern Parental Behaviour","volume":"509","author":"Wu","year":"2014","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/BF00427607","article-title":"Drug Self-Administration and Sleep-Awake Activity in Rats Dependent on Morphine, Methadone, or\/-Alpha-Acetylmethadol","volume":"47","author":"Moreton","year":"1976","journal-title":"Psychopharmacology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/S0885-3924(02)00531-6","article-title":"Relationships Among Morphine Metabolism, Pain and Side Effects During Long-Term Treatment: An Update","volume":"25","author":"Andersen","year":"2003","journal-title":"J. Pain Symptom Manag."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0006-8993(00)02304-0","article-title":"Opioid Induced Non-Photic Phase Shifts of Hamster Circadian Activity Rhythms","volume":"873","author":"Byku","year":"2000","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0006-8993(83)90627-3","article-title":"Circadian Variations in \u03b2-Endorphin Concentrations in Pituitary and in Some Brain Nuclei of the Adult Male Rat","volume":"261","author":"Kerdelhue","year":"1983","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ynstr.2016.09.001","article-title":"Interaction between Circadian Rhythms and Stress","volume":"6","author":"Koch","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/0165-0173(93)90013-P","article-title":"The Neural Basis of Drug Craving: An Incentive-Sensitization Theory of Addiction","volume":"18","author":"Robinson","year":"1993","journal-title":"Brain Res. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1476-5381.1972.tb06866.x","article-title":"Time-Dose Relationships for Locomotor Activity Effects of Morphine after Acute or Repeated Treatment","volume":"46","author":"Babbini","year":"1972","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0014-2999(02)01812-5","article-title":"Lack of Reward and Locomotor Stimulation Induced by Heroin in \u03bc-Opioid Receptor-Deficient Mice","volume":"446","author":"Contarino","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e44358","DOI":"10.7554\/eLife.44358","article-title":"Distinct IpRGC Subpopulations Mediate Light\u2019s Acute and Circadian Effects on Body Temperature and Sleep","volume":"8","author":"Rupp","year":"2019","journal-title":"eLife"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"74","DOI":"10.2741\/3677","article-title":"Central Neural Pathways for Thermoregulation","volume":"16","author":"Morrison","year":"2011","journal-title":"Front. Biosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R1493","DOI":"10.1152\/ajpregu.1999.277.5.R1493","article-title":"Relationship between the Daily Rhythms of Locomotor Activity and Body Temperature in Eight Mammalian Species","volume":"277","author":"Refinetti","year":"1999","journal-title":"Am. J. Physiol. -Regul. Integr. Comp. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00213-013-3298-z","article-title":"Effects of Repeated Exposure to Morphine in Adolescent and Adult Male C57BL\/6J Mice: Age-Dependent Differences in Locomotor Stimulation, Sensitization, and Body Weight Loss","volume":"231","author":"Koek","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0031-9384(97)00546-5","article-title":"Diurnally Changing Effects of Locomotor Activity on Body Temperature in Laboratory Mice","volume":"63","author":"Weinert","year":"1998","journal-title":"Physiol. Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1034\/j.1600-0773.2003.t01-1-920202.x","article-title":"Morphine and D-Amphetamine Nullify Each Others\u2019 Hypothermic Effects in Mice","volume":"92","author":"Baker","year":"2003","journal-title":"Pharmacol. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0376-8716(96)01295-1","article-title":"Antisense Confirmation of \u03bc- and \u03ba-Opioid Receptor Mediation of Morphine\u2019s Effects on Body Temperature in Rats","volume":"43","author":"Chen","year":"1996","journal-title":"Drug Alcohol Depend."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0091-3057(00)00457-3","article-title":"The Possible Cross-Tolerance between Morphine- and Nicotine-Induced Hypothermia in Mice","volume":"68","author":"Zarrindast","year":"2001","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1124\/jpet.102.037655","article-title":"Functional Effects of Systemically Administered Agonists and Antagonists of \u03bc, \u03b4, and \u03ba Opioid Receptor Subtypes on Body Temperature in Mice","volume":"302","author":"Baker","year":"2002","journal-title":"J. Pharm. Exp."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1007\/s002100100404","article-title":"Loss of Locomotor Sensitisation in Response to Morphine in D1 Receptor Deficient Mice","volume":"363","author":"Becker","year":"2001","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1007\/s00213-011-2432-z","article-title":"Morphine-Induced Motor Stimulation, Motor Incoordination, and Hypothermia in Adolescent and Adult Mice","volume":"219","author":"Koek","year":"2012","journal-title":"Psychopharmacology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00213-011-2223-6","article-title":"Chronic and Intermittent Morphine Treatment Differently Regulates Opioid and Dopamine Systems: A Role in Locomotor Sensitization","volume":"216","author":"Noble","year":"2011","journal-title":"Psychopharmacology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/0306-3623(92)90315-B","article-title":"Morphine Stimulates Locomotor Activity by an Indirect Dopaminergic Mechanism: Possible D-1 and D-2 Receptor Involvement","volume":"23","author":"Zarrindast","year":"1992","journal-title":"Gen. Pharmacol. Vasc. Syst."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.neubiorev.2011.12.012","article-title":"The Use of a Running Wheel to Measure Activity in Rodents: Relationship to Energy Balance, General Activity, and Reward","volume":"36","author":"Novak","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuron.2010.05.023","article-title":"Melanopsin-Expressing Retinal Ganglion-Cell Photoreceptors: Cellular Diversity and Role in Pattern Vision","volume":"67","author":"Ecker","year":"2010","journal-title":"Neuron"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Maloney, R., Quattrochi, L., Yoon, J., Souza, R., and Berson, D. (2022). Efficacy and Specificity of Melanopsin Reporters for Retinal Ganglion Cells. bioRxiv.","DOI":"10.1101\/2022.04.26.489554"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"374","DOI":"10.3109\/07420528.2016.1151025","article-title":"Age-Related Changes in Photosensitive Melanopsin-Expressing Retinal Ganglion Cells Correlate with Circadian Rhythm Impairments in Sighted and Blind Rats","volume":"33","author":"Lax","year":"2016","journal-title":"Chronobiol. Int."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Lax, P., Ortu\u00f1o-Lizar\u00e1n, I., Maneu, V., Vidal-Sanz, M., and Cuenca, N. (2019). Photosensitive Melanopsin-Containing Retinal Ganglion Cells in Health and Disease: Implications for Circadian Rhythms. IJMS, 20.","DOI":"10.3390\/ijms20133164"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00441-021-03500-0","article-title":"de L. Opsins Outside the Eye and the Skin: A More Complex Scenario than Originally Thought for a Classical Light Sensor","volume":"385","author":"Moraes","year":"2021","journal-title":"Cell Tissue Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"39","DOI":"10.14740\/jnr427w","article-title":"Transcranial Light Alters Melanopsin and Monoamine Production in Mouse ( Mus Musculus ) Brain","volume":"7","author":"Flyktman","year":"2017","journal-title":"J. Neurol. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.cell.2018.07.028","article-title":"Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain","volume":"174","author":"Saunders","year":"2018","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jneumeth.2003.10.008","article-title":"Activity Patterns as a Correlate for Sleep\u2013Wake Behaviour in Mice","volume":"133","author":"Storch","year":"2004","journal-title":"J. Neurosci. Methods"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S0149-7634(00)00015-4","article-title":"Sex Differences in Thermal Nociception and Morphine Antinociception in Rodents Depend on Genotype","volume":"24","author":"Mogil","year":"2000","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.pbb.2006.11.022","article-title":"Sex Differences in Locomotor Effects of Morphine in the Rat","volume":"85","author":"Craft","year":"2006","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5100","DOI":"10.1523\/JNEUROSCI.22-12-05100.2002","article-title":"\u03bc-Opioid Receptor-Mediated Antinociceptive Responses Differ in Men and Women","volume":"22","author":"Zubieta","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Cleymaet, A.M., Berezin, C.-T., and Vigh, J. (2021). Endogenous Opioid Signaling in the Mouse Retina Modulates Pupillary Light Reflex. IJMS, 22.","DOI":"10.3390\/ijms22020554"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1161\/01.CIR.0000121422.85989.BD","article-title":"Morphine-Tolerant Mice Exhibit a Profound and Persistent Cardioprotective Phenotype","volume":"109","author":"Peart","year":"2004","journal-title":"Circulation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5115","DOI":"10.1038\/s41467-021-25378-w","article-title":"The Retinal IpRGC-Preoptic Circuit Mediates the Acute Effect of Light on Sleep","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1365-2818.2006.01706.x","article-title":"A Guided Tour into Subcellular Colocalization Analysis in Light Microscopy","volume":"224","author":"Bolte","year":"2006","journal-title":"J. Microsc."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1093\/bioinformatics\/btt276","article-title":"TANGO: A Generic Tool for High-Throughput 3D Image Analysis for Studying Nuclear Organization","volume":"29","author":"Ollion","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0091-3057(03)00090-X","article-title":"The Modulatory Actions of Dopamine D2\/3 Agonists and Antagonists on the Locomotor-Activating Effects of Morphine and Caffeine in Mice","volume":"75","author":"Cook","year":"2003","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0301-0082(00)00033-2","article-title":"Pharmacology and Behavioral Pharmacology of the Mesocortical Dopamine System","volume":"63","author":"Tzschentke","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1037\/0033-295X.94.4.469","article-title":"A Psychomotor Stimulant Theory of Addiction","volume":"94","author":"Wise","year":"1987","journal-title":"Psychol. Rev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15870\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:40:56Z","timestamp":1760146856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":82,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415870"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415870","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}