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This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behaviour. While cocaine reinforcement depends on the mesolimbic system, well\u2010established cocaine seeking is dependent on dorsolateral striatum (<jats:styled-content style=\"fixed-case\">aDLS<\/jats:styled-content>) dopamine\u2010dependent mechanisms which are disrupted by N\u2010acetylcysteine, through normalisation of corticostriatal glutamate homeostasis. However, it is unknown whether a functional recruitment of <jats:styled-content style=\"fixed-case\">aDLS<\/jats:styled-content> dopamine\u2010dependent control over instrumental responding also occurs for heroin seeking, even though heroin reinforcement does not depend on the mesolimbic dopamine system. Lister Hooded rats acquired heroin self\u2010administration and were subsequently trained to seek heroin daily over prolonged periods of time under the control of drug\u2010paired cues, as measured under a second\u2010order schedule of reinforcement. At different stages of training, that is, early on and when heroin seeking behaviour was well established, we measured the sensitivity of drug\u2010seeking responses to either bilateral <jats:styled-content style=\"fixed-case\">aDLS<\/jats:styled-content> infusions of the dopamine receptor antagonist \u03b1\u2010flupenthixol (5, 10 and 15 \u03bcg\/side) or systemic administration of N\u2010acetylcysteine (30, 60 and 90\u00a0mg\/kg). The results demonstrate that control over heroin seeking behaviour devolves to <jats:styled-content style=\"fixed-case\">aDLS<\/jats:styled-content> dopamine\u2010dependent mechanisms after extended training. Further <jats:styled-content style=\"fixed-case\">aDLS<\/jats:styled-content>\u2010dependent well\u2010established, cue\u2010controlled heroin seeking was disrupted by N\u2010acetylcysteine. Comparison with previous data on cocaine suggests that the development of drug seeking habits and the alteration of corticostriatal glutamate homeostasis, which is restored by N\u2010acetylcysteine, are quantitatively similar between heroin and cocaine.<\/jats:p>","DOI":"10.1111\/ejn.13894","type":"journal-article","created":{"date-parts":[[2018,3,8]],"date-time":"2018-03-08T00:12:42Z","timestamp":1520467962000},"page":"2036-2044","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Heroin seeking becomes dependent on dorsal striatal dopaminergic mechanisms and can be decreased by N\u2010acetylcysteine"],"prefix":"10.1111","volume":"50","author":[{"given":"Ritchy","family":"Hodebourg","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Montreal Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer 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