• Psychopharmacology · Mar 2013

    The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats.

    • Pietro Cottone, Attilio Iemolo, Aditi R Narayan, Jina Kwak, Duncan Momaney, and Valentina Sabino.
    • Department of Pharmacology, Laboratory of Addictive Disorders, Boston University School of Medicine, 72 E Concord St., R-618, Boston, MA 02118, USA. cottone@bu.edu
    • Psychopharmacology (Berl.). 2013 Mar 1; 226 (1): 127-38.

    RationaleImpulsive behavior is categorically differentiated between impulsive action, the inability to withhold from acting out a response, and impulsive choice, the greater preference for an immediate and smaller reward over a delayed but more advantageous reward. While the effects of N-methyl-D-aspartic acid (NMDA) receptor antagonists on impulsive action have been extensively characterized, there are very few and conflicting reports on the effects of this class of drugs on impulsive choice.ObjectivesUsing a modified adjusting delay task, we investigated the effects of uncompetitive and competitive blockade of NMDA receptors on impulsive choice.MethodsMale Wistar rats were trained in a modified adjusting delay task, which involved repeated choice between a low reinforcing solution delivered immediately and a highly reinforcing solution delivered after a variable delay. Rats were then administered either the NMDA receptor uncompetitive antagonists ketamine or memantine, or the competitive antagonists D-AP-5 or CGS 19755.ResultsKetamine treatment dose-dependently increased impulsive choice, and this effect was selective for low-impulsive but not high-impulsive rats. Similarly, memantine treatment dose-dependently increased impulsive choice with a preferential effect for low-impulsive rats. While D-AP-5 treatment did not affect impulsive choice, CGS 19755 increased impulsivity, however, at the same doses at which it caused a marked response inhibition.ConclusionsNMDA receptor uncompetitive, but not competitive, antagonists significantly increased impulsive choice, preferentially in low-impulsive rats. These findings demonstrate that the effects of NMDA receptor blockade on impulsive choice are not generalizable and depend on the specific mechanism of action of the antagonist used.

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