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Mark J. Ferris, Erin S. Calipari, James R. Melchior, David C. S. Roberts, Rodrigo A. España and Sara R. Jones Paradoxical tolerance to cocaine after initial supersensitivity in drug-use-prone animals European Journal of Neuroscience 38

Article first published online: 3 JUN 2013 | DOI: 10.1111/ejn.12266

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There is great interest in outlining biological factors and behavioral characteristics that either predispose or predict vulnerability to substance use disorders. We used cocaine self-administration under a fixed-ratio one schedule followed by fast scan cyclic voltammetry in brain slices to measure sub-second DA release and uptake parameters in drug-use prone and resistant phenotypes. We show a supersensitivity in the ability of cocaine to inhibit dopamine uptake following acute administration in animals with higher locomotor response to a novel environment. Following a history of cocaine self-administration, however, tolerance in the ability of cocaine to inhibit dopamine uptake coexists with a behavioral phenotype that is defined by increased preoccupation with cocaine as measured by rapid acquisition and early high intake.

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