title: The uncompetitive NMDA receptor antagonists ketamine and memantine preferentially increase the choice for a small, immediate reward in low-impulsive rats.
abstract: BACKGROUND
  Impulsive 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.
  
  
  OBJECTIVE
  Using a modified adjusting delay task, we investigated the effects of uncompetitive and competitive blockade of NMDA receptors on impulsive choice.
  
  
  METHODS
  Male 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.
  
  
  RESULTS
  Ketamine 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.
  
  
  CONCLUSIONS
  NMDA 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.
authors.affiliation: 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
authors.forename: Pietro
authors.initials: P
authors.lastname: Cottone
authors.forename: Attilio
authors.initials: A
authors.lastname: Iemolo
authors.forename: Aditi R
authors.initials: AR
authors.lastname: Narayan
authors.forename: Jina
authors.initials: J
authors.lastname: Kwak
authors.forename: Duncan
authors.initials: D
authors.lastname: Momaney
authors.forename: Valentina
authors.initials: V
authors.lastname: Sabino
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D007175:Impulsive Behavior / Q000378:metabolism / Q000523:psychology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012201:Reward
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D008559:Memantine