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The adenosine 2A<\/jats:styled-content>(A<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub><\/jats:styled-content>) receptor presents a potential therapeutic target forMETH<\/jats:styled-content>abuse due to its modulatory effects on striatal dopamine and glutamate transmission. Notably,A<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub><\/jats:styled-content>receptor signalling has been implicated in the rewarding effects of alcohol, cocaine and opiates; yet, the role of this receptor inMETH<\/jats:styled-content>consumption and seeking is essentially unknown. Therefore, the current study usedA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub><\/jats:styled-content>knockout (KO<\/jats:styled-content>) mice to assess the role ofA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub><\/jats:styled-content>in behaviours relevant toMETH<\/jats:styled-content>addiction.METH<\/jats:styled-content>conditioned place preference was absent inA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub>KO<\/jats:styled-content>mice compared with wild\u2010type (WT<\/jats:styled-content>) littermates. RepeatedMETH<\/jats:styled-content>treatment produced locomotor sensitization in both genotypes; however, sensitization was attenuated inA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub>KO<\/jats:styled-content>mice in a dose\u2010related manner.METH<\/jats:styled-content>intravenous self\u2010administration was intact inA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub>KO<\/jats:styled-content>mice over a range of doses and schedules of reinforcement. However, the motivation to self\u2010administer was reduced inA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub>KO<\/jats:styled-content>mice. Regression analysis further supported the observation that the motivation to self\u2010administerMETH<\/jats:styled-content>was reduced inA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub>KO<\/jats:styled-content>mice even when self\u2010administration was similar toWT<\/jats:styled-content>mice. Sucrose self\u2010administration was also reduced inA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub>KO<\/jats:styled-content>mice but only at higher schedules of reinforcement. Collectively, these data suggest thatA<\/jats:styled-content>2<\/jats:sub>A<\/jats:sub><\/jats:styled-content>signalling is critically required to integrate rewarding and motivational properties of bothMETH<\/jats:styled-content>and natural rewards.<\/jats:p>","DOI":"10.1111\/adb.12225","type":"journal-article","created":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T11:18:57Z","timestamp":1421925537000},"page":"407-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Adenosine 2A<\/scp>receptors modulate reward behaviours for methamphetamine"],"prefix":"10.1111","volume":"21","author":[{"given":"Rose","family":"Chesworth","sequence":"first","affiliation":[{"name":"Behavioural Neuroscience Division Florey Institute of Neuroscience and Mental Health Australia"},{"name":"Florey Department of Neuroscience and Mental Health University of Melbourne 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