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Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 \u00d7 25 mg\/kg\/injection, 2\u2010h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D<jats:sub>1<\/jats:sub>\u2010like (SCH\u201023380) or D<jats:sub>2<\/jats:sub>\u2010like (eticlopride) antagonists blocked mephedrone\u2010induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling.<jats:bold>Synapse 68:634\u2013640, 2014<\/jats:bold>. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/syn.21778","type":"journal-article","created":{"date-parts":[[2014,8,25]],"date-time":"2014-08-25T14:33:50Z","timestamp":1408977230000},"page":"634-640","source":"Crossref","is-referenced-by-count":1,"title":["Mephedrone alters basal ganglia and limbic dynorphin systems"],"prefix":"10.1002","volume":"68","author":[{"given":"Christopher L.","family":"German","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology College of Pharmacy, University of Utah Salt Lake City Utah"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario 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