{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:36:40Z","timestamp":1792805800306,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["2018R1A5A2025272"],"award-info":[{"award-number":["2018R1A5A2025272"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["2019R1A2C1002555"],"award-info":[{"award-number":["2019R1A2C1002555"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)","award":["2020R1C1C1006534"],"award-info":[{"award-number":["2020R1C1C1006534"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Korean Medical Device Development Fund grant by the Korean government (the Ministy of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health &amp; Welfare, the Ministry of Food and Drug Safety)","award":["9991006790, KMDF_PR_20200901_0117"],"award-info":[{"award-number":["9991006790, KMDF_PR_20200901_0117"]}],"id":[{"id":"https:\/\/ror.org\/008nkqk13","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Drug addiction has become a worldwide problem, affecting millions of people across the globe. While the majority of mechanistic studies on drug addiction have been focused on the central nervous system, including the mesolimbic dopamine system, the peripheral actions of drugs of abuse remain largely unknown. Our preliminary study found that the systemic injection of cocaine increased peripheral skin temperature. This led us to our present study, which investigated the mechanisms underlying the increase in peripheral temperature following cocaine injection. Male Sprague Dawley rats were anesthetized with pentobarbital sodium, and peripheral skin temperature measurements were taken using a thermocouple needle microprobe and an infrared thermal camera. Cocaine injection caused an acute rise in peripheral body temperature, but not core body temperature, about 10 min after injection, and the temperature increases were occluded by systemic injection of dopamine D2 receptor antagonist L741,626, but not D1 receptor antagonist SCH23390. In addition, systemic administration of bromocriptine, a dopamine D2 receptor agonist, significantly increased peripheral temperature. Infrared thermal imaging showed that the thermal increases following cocaine injection were predominantly in the distal areas of the forelimbs and hindlimbs, relative to core body temperature. Treatment with cocaine or bromocriptine decreased the size of skin blood vessels without affecting the expression of dopamine D2 receptors. These results suggest that increased peripheral temperature in skin following cocaine injection is associated with the activation of the dopamine D2 receptor.<\/jats:p>","DOI":"10.3390\/life12020143","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T08:20:57Z","timestamp":1642580457000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Increase in Peripheral Temperature following Cocaine Administration Is Mediated through Activation of Dopamine D2 Receptor in Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Suchan","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonhee","family":"Ryu","sequence":"additional","affiliation":[{"name":"Korean Medicine Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Kyun","family":"Bang","sequence":"additional","affiliation":[{"name":"Korean Medicine Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Byeol","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"DanBi","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-0764","authenticated-orcid":false,"given":"Sang Chan","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Research Center, College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong Hyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Korean Medicine, Daegu Haany University, Daegu 42158, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Canton, H. (2021). United Nations Office on Drugs and Crime\u2014UNODC. The Europa Directory of International Organizations, Routledge.","DOI":"10.4324\/9781003179900-33"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/157015911795017245","article-title":"Understanding the global problem of drug addiction is a challenge for IDARS scientists","volume":"9","author":"Ali","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15057","DOI":"10.1021\/jp900963n","article-title":"Mechanism for cocaine blocking the transport of dopamine: Insights from molecular modeling and dynamics simulations","volume":"113","author":"Huang","year":"2009","journal-title":"J. Phys. Chem. B"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/10673220490910844","article-title":"Neurobiologic processes in drug reward and addiction","volume":"12","author":"Adinoff","year":"2004","journal-title":"Harv. Rev. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3109\/03091902.2014.902513","article-title":"Remote physiological monitoring of acute cocaine exposure","volume":"38","author":"Yoon","year":"2014","journal-title":"J. Med. Eng. Technol."},{"key":"ref_6","first-page":"122","article-title":"The emergency care of cocaine intoxications","volume":"67","author":"Vroegop","year":"2009","journal-title":"Neth. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1161\/CIRCULATIONAHA.110.940569","article-title":"Cardiovascular effects of cocaine","volume":"122","author":"Schwartz","year":"2010","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1161\/01.CIR.100.5.497","article-title":"Cocaine stimulates the human cardiovascular system via a central mechanism of action","volume":"100","author":"Vongpatanasin","year":"1999","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1172\/JCI115135","article-title":"Effects of cocaine on excitation-contraction coupling of aortic smooth muscle from the ferret","volume":"87","author":"Egashira","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1161\/CIRCULATIONAHA.113.002937","article-title":"Cocaine-induced vasoconstriction in the human coronary microcirculation: New evidence from myocardial contrast echocardiography","volume":"128","author":"Gurudevan","year":"2013","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJM198912073212301","article-title":"Cocaine-induced coronary-artery vasoconstriction","volume":"321","author":"Lange","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nrn3043","article-title":"Differentiating the rapid actions of cocaine","volume":"12","author":"Wise","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1000337","DOI":"10.4172\/2155-9554.1000337","article-title":"Dermatologic Signs and Symptoms of Substance Abuse","volume":"7","author":"Raiker","year":"2016","journal-title":"J. Clin. Exp. Dermatol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.clindermatol.2010.03.024","article-title":"The effects of alcohol and drug abuse on the skin","volume":"28","author":"Liu","year":"2010","journal-title":"Clin. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.4172\/2161-0940.1000197","article-title":"Daily changes of body temperature and heart rate are modulated after estradiol depletion in female rats","volume":"6","author":"Marui","year":"2016","journal-title":"Anat Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.appet.2016.05.008","article-title":"Systemic injection of the DAD1 antagonist SCH 23390 reduces saccharin seeking in rats","volume":"105","author":"Aoyama","year":"2016","journal-title":"Appetite"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.neuron.2016.03.030","article-title":"Microglial TNF-\u03b1 suppresses cocaine-induced plasticity and behavioral sensitization","volume":"90","author":"Lewitus","year":"2016","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0006-8993(86)91178-9","article-title":"Synergistic effects of D1 and D2 dopamine agonists on turning behaviour in rats","volume":"384","author":"Robertson","year":"1986","journal-title":"Brain Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/0006-291X(92)90640-7","article-title":"Production and characterization of a monoclonal antibody to dopamine D2 receptor: Comparison with a polyclonal antibody to a different epitope","volume":"184","author":"Farooqui","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1007\/s00726-017-2408-3","article-title":"Validation of dopamine receptor DRD1 and DRD2 antibodies using receptor deficient mice","volume":"49","author":"Stojanovic","year":"2017","journal-title":"Amino Acids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fphar.2021.624127","article-title":"Cocaine Reduces the Neuronal Population While Upregulating Dopamine D2-Receptor-Expressing Neurons in Brain Reward Regions: Sex-Effects","volume":"12","author":"Clare","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Navarro, G., Moreno, E., Bonaventura, J., Brugarolas, M., Farre, D., Aguinaga, D., Mallol, J., Cortes, A., Casado, V., and Llu\u00eds, C. (2013). Cocaine inhibits dopamine D2 receptor signaling via sigma-1-D2 receptor heteromers. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061245"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S0002-9343(96)00453-6","article-title":"Cocaine effects on digital blood flow and diffusing capacity for carbon monoxide among chronic cocaine users","volume":"102","author":"Sullivan","year":"1997","journal-title":"Am. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1124\/jpet.102.039867","article-title":"Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes","volume":"303","author":"Millan","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1124\/jpet.102.039875","article-title":"Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. II. Agonist and antagonist properties at subtypes of dopamine D2-like receptor and \u03b11\/\u03b12-adrenoceptor","volume":"303","author":"Cussac","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1124\/jpet.102.039883","article-title":"Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT1 and 5-HT2, receptor subtypes","volume":"303","author":"Cussac","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"785","DOI":"10.7326\/0003-4819-136-11-200206040-00006","article-title":"Mechanism of cocaine-induced hyperthermia in humans","volume":"136","author":"Crandall","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000138648","article-title":"Cocaine and body temperature in the rat: Effects of ambient temperature","volume":"40","author":"Lomax","year":"1990","journal-title":"Pharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/0006-8993(84)90947-8","article-title":"Changes in the hypothalamic mechanisms involved in the control of body temperature induced by the early thermal environment","volume":"290","author":"Ferguson","year":"1984","journal-title":"Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/BF00169004","article-title":"Stimulation of the nigrostriatal dopamine system inhibits both heat production and heat loss mechanisms in rats","volume":"346","author":"Lin","year":"1992","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/0091-3057(90)90095-Y","article-title":"Cocaine and body temperature in the rat: Effect of exercise","volume":"36","author":"Lomax","year":"1990","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.physbeh.2005.02.002","article-title":"Brain and body temperature homeostasis during sodium pentobarbital anesthesia with and without body warming in rats","volume":"84","author":"Kiyatkin","year":"2005","journal-title":"Physiol. Behav."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1749-6632.2009.05144.x","article-title":"Cocaine-induced neuroadaptations in glutamate transmission: Potential therapeutic targets for craving and addiction","volume":"1187","author":"Schmidt","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1151\/spp05314","article-title":"The neurobiology of cocaine addiction","volume":"3","author":"Nestler","year":"2005","journal-title":"Sci. Pract. Perspect."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vaughn, A.R., Davis, M.J., Sivamani, R.K., and Isseroff, R.R. (2017). A Concise Review of the Conflicting Roles of Dopamine-1 versus Dopamine-2 Receptors in Wound Healing. Molecules, 23.","DOI":"10.3390\/molecules23010050"},{"key":"ref_36","first-page":"789","article-title":"Dopaminergic receptors in the human skin","volume":"26","author":"Tammaro","year":"2012","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1111\/j.0022-202X.2005.23873.x","article-title":"Dopamine D2-like receptor agonists accelerate barrier repair and inhibit the epidermal hyperplasia induced by barrier disruption","volume":"125","author":"Fuziwara","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.coph.2009.09.011","article-title":"Heteromerization of dopamine D2 receptors with dopamine D1 or D5 receptors generates intracellular calcium signaling by different mechanisms","volume":"10","author":"Hasbi","year":"2010","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0014-2999(93)90177-J","article-title":"Differential effects of Mandevilla velutina compounds on paw oedema induced by phospholipase A2 and phospholipase C","volume":"243","author":"Neves","year":"1993","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","first-page":"518","article-title":"Role of phospholipase C and phospholipase A2 in the nitric oxide-independent vasodilator effect of bradykinin in the rat perfused heart","volume":"278","author":"Fulton","year":"1996","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15248","DOI":"10.1073\/pnas.0606578103","article-title":"Activation, internalization, and recycling of the serotonin 2A receptor by dopamine","volume":"103","author":"Bhattacharyya","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/syn.10273","article-title":"Direct activation by dopamine of recombinant human 5-HT1A receptors: Comparison with human 5-HT2C and 5-HT3 receptors","volume":"50","author":"Oz","year":"2003","journal-title":"Synapse"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1046\/j.0953-816x.2001.01616.x","article-title":"D2-like dopamine receptor activation excites rat dorsal raphe 5-HT neurons in vitro","volume":"14","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0014-2999(00)00585-9","article-title":"Involvement of the 5-HT2 receptor in hyperthermia induced by p-chloroamphetamine, a serotonin-releasing drug in mice","volume":"403","author":"Sugimoto","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0893-133X(02)00318-4","article-title":"Serotonin 1A receptor activation and hypothermia in humans: Lack of evidence for a presynaptic mediation","volume":"27","author":"Blier","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/0028-3908(86)90101-2","article-title":"Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat: Evidence for opposing roles of 5-HT2 and 5-HT1A receptors","volume":"25","author":"Gudelsky","year":"1986","journal-title":"Neuropharmacology"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/2\/143\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:04:05Z","timestamp":1760133845000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/2\/143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,19]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["life12020143"],"URL":"https:\/\/doi.org\/10.3390\/life12020143","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,19]]}}}