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The anticholinergic scopolamine interferes with learning when tested in rats, which coincides with a negative blood-oxygen-level-dependent (BOLD) change in the prefrontal cortex (PFC) as demonstrated by fMRI. The peripherally acting butylscopolamine also evokes a learning deficit in a water-labyrinth test and provokes a negative BOLD signal in the PFC. Donepezil\u2014a highly CNS-penetrating Cholinesterase inhibitor\u2014prevents the negative BOLD and cognitive deficits regardless whether the provoking agent is scopolamine or butylscopolamine. Interestingly, the non-BBB-penetrating Cholinesterase inhibitor neostigmine also prevents or substantially inhibits those cognitive and fMRI changes. Intact cerebral blood flow and optimal metabolism are crucial for the normal functioning of neurons and other cells in the brain. Drugs that are not BBB penetrating yet act on the CNS highlight the importance of unimpaired circulation, and point to the cerebral vasculature as a primary target for drug action in diseases where impaired circulation and consequently suboptimal energy metabolism are followed by upstream pathologic events.<\/jats:p>","DOI":"10.1038\/jcbfm.2014.47","type":"journal-article","created":{"date-parts":[[2014,3,19]],"date-time":"2014-03-19T05:02:05Z","timestamp":1395205325000},"page":"995-1000","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Vascular Action as the Primary Mechanism of Cognitive Effects of Cholinergic, CNS-Acting Drugs, a Rat phMRI BOLD Study"],"prefix":"10.1177","volume":"34","author":[{"given":"P\u00e1l","family":"Kocsis","sequence":"first","affiliation":[{"name":"Pharmacology and Drug Safety Research, Gedeon Richter Ltd. 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