{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:27:59Z","timestamp":1781796479001,"version":"3.54.5"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003065","name":"University of Vienna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Among psychostimulants, the dopamine transporter ligands amphetamine and cocaine display the highest addictive potential; the adenosine receptor antagonist caffeine is most widely consumed but less addictive. Psychostimulant actions of amphetamine were correlated with its ability to orchestrate ventral tegmental dopamine neuron activity with contrasting shifts in firing after single vs repeated administration. Whether caffeine might impinge on dopamine neuron activity has remained elusive.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Population activity of ventral tegmental area dopamine neurons was determined by single-unit extracellular recordings and set in relation to mouse behavior in locomotion and conditioned place preference experiments, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A single dose of caffeine reduced population activity as did amphetamine and the selective adenosine A2A antagonist KW-6002, but not the A1 antagonist DPCPX. Repeated administration\u2009of\u2009KW-6002\u2009or\u2009amphetamine\u2009led\u2009to\u2009drug-conditioned\u2009place\u2009preference\u2009and to\u2009unaltered\u2009or\u2009even\u2009enhanced\u2009population\u2009activity.\u2009Recurrent\u2009injection\u2009of\u2009caffeine\u2009or DPCPX, in contrast, failed to cause conditioned place preference and persistently reduced population\u2009activity.\u2009Subsequent\u2009to\u2009repetitive\u2009drug\u2009administration,\u2009re-exposure\u2009to amphetamine or KW-6002, but not to caffeine or DPCPX, was able to reduce population activity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Behavioral sensitization to amphetamine is attributed to persistent activation of ventral tegmental area dopamine neurons via the ventral hippocampus. Accordingly, a switch from acute A2A receptor-mediated reduction of dopamine neuron population activity to enduring A1 receptor-mediated suppression is correlated with tolerance rather than sensitization in response to repeated caffeine intake.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyab049","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T07:16:55Z","timestamp":1626333415000},"page":"832-841","source":"Crossref","is-referenced-by-count":11,"title":["Orchestration of Dopamine Neuron Population Activity in the Ventral Tegmental Area by Caffeine: Comparison With Amphetamine"],"prefix":"10.1093","volume":"24","author":[{"given":"Ornella","family":"Valenti","sequence":"first","affiliation":[{"name":"Division of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Zambon","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Boehm","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"2021102310543564600_CIT0001a","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.biopsych.2014.04.014","article-title":"Restoring mood balance in depression: ketamine reverses deficit in dopamine-dependent synaptic plasticity","volume":"76","author":"Belujon","year":"2014","journal-title":"Biol Psychiatry"},{"key":"2021102310543564600_CIT0001","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1093\/ijnp\/pyx056","article-title":"Dopamine system dysregulation in major depressive disorders","volume":"20","author":"Belujon","year":"2017","journal-title":"Int J Neuropsychopharmacol"},{"key":"2021102310543564600_CIT0002","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/38160","article-title":"Caffeine alters plasma adenosine levels","volume":"389","author":"Conlay","year":"1997","journal-title":"Nature"},{"key":"2021102310543564600_CIT0003","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.neuron.2019.12.026","article-title":"Dopamine-evoked synaptic regulation in the nucleus accumbens requires astrocyte activity","volume":"105","author":"Corkrum","year":"2020","journal-title":"Neuron"},{"key":"2021102310543564600_CIT0004","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1038\/nprot.2006.279","article-title":"Drug-induced conditioned place preference and aversion in mice","volume":"1","author":"Cunningham","year":"2006","journal-title":"Nat Protoc"},{"key":"2021102310543564600_CIT0005","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nn.4482","article-title":"Circuit specificity in the inhibitory architecture of the VTA regulates cocaine-induced behavior","volume":"20","author":"Edwards","year":"2017","journal-title":"Nat Neurosci"},{"key":"2021102310543564600_CIT0006","first-page":"1465","article-title":"The stimulant effects of caffeine on locomotor behaviour in mice are mediated through\u2009its\u2009blockade\u2009of\u2009adenosine\u2009A(2A)\u2009receptors.","volume":"129","author":"El Yacoubi","year":"2000","journal-title":"Br\u2009J\u2009Pharmacol"},{"key":"2021102310543564600_CIT0007","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/j.1471-4159.2007.05196.x","article-title":"An update on the mechanisms of the psychostimulant effects of caffeine","volume":"105","author":"Ferr\u00e9","year":"2008","journal-title":"J Neurochem"},{"issue":"Suppl 1","key":"2021102310543564600_CIT0008","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.3233\/JAD-2010-1400","article-title":"Role of the central ascending neurotransmitter systems in the psychostimulant effects of caffeine","volume":"20","author":"Ferr\u00e9","year":"2010","journal-title":"J. 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