title: Continuous exposure to dizocilpine facilitates the acquisition and escalation of cocaine consumption in male Sprague-Dawley rats.
abstract: BACKGROUND
  Blocking N-methyl-d-aspartate (NMDA) glutamate receptors (NMDARs) prevents cocaine locomotor sensitization, but facilitates escalation of cocaine self-administration and produces ambiguous effects on acquisition of cocaine self-administration. This study used a recently described model of acquisition and escalation to test the hypothesis that continuous NMDAR antagonism functionally increases the effects of a given dose of cocaine.
  
  
  METHODS
  We assessed acquisition of cocaine self-administration (0.6 mg/kg/infusion) in rats treated continuously with either vehicle or the NMDAR antagonist dizocilpine (0.4 mg/kg/day) for 14 consecutive 2h fixed ratio 1 (FR1) sessions. In a separate experiment that assessed the effect of dizocilpine treatment on escalation of cocaine self-administration, rats acquired cocaine self-administration (0.6 mg/kg/infusion) prior to vehicle or dizocilpine treatment. Then, immediately post-acquisition, rats were treated continuously with either vehicle or dizocilpine and allowed to self-administer either 0.6 or 1.2mg/kg/infusion cocaine for an additional seven consecutive 2h FR1 sessions.
  
  
  RESULTS
  Relative to vehicle-treated rats, a significantly greater percentage of dizocilpine-treated rats acquired cocaine self-administration. During the escalation experiment, both vehicle- and dizocilpine-treated rats escalated intake of 1.2mg/kg/infusion cocaine. Whereas vehicle-treated rats exhibited stable intake of 0.6 mg/kg/infusion cocaine, dizocilpine-treated rats escalated intake of this moderate cocaine dose to levels indistinguishable from intake levels produced by self-administration of the high cocaine dose (i.e., 1.2mg/kg/infusion).
  
  
  CONCLUSIONS
  These findings suggest that chronic NMDAR blockade potentiates, rather than attenuates, cocaine's effects and argue for reconsideration of the role of NMDARs in cocaine "addiction-like" behavior.
authors.affiliation: Department of Psychology, University of Colorado Denver, 1200 Larimer Street, Denver, CO 80204, United States. Electronic address: richard.allen@ucdenver.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Allen
authors.affiliation: Department of Psychology, University of Colorado Denver, 1200 Larimer Street, Denver, CO 80204, United States.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mandt
authors.affiliation: Department of Psychology, University of Colorado Denver, 1200 Larimer Street, Denver, CO 80204, United States.
authors.forename: Jillian
authors.initials: J
authors.lastname: Jaskunas
authors.affiliation: Department of Psychology, University of Colorado Denver, 1200 Larimer Street, Denver, CO 80204, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hackley
authors.affiliation: Department of Psychology, University of Colorado Denver, 1200 Larimer Street, Denver, CO 80204, United States.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Shickedanz
authors.affiliation: Department of Psychology, University of Colorado Denver, 1200 Larimer Street, Denver, CO 80204, United States.
authors.forename: David
authors.initials: D
authors.lastname: Bergkamp
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000209:etiology* / Q000523:psychology; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D055104:Infusions, Subcutaneous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D003042:Cocaine
keywords: Acquisition; Cocaine self-administration; Dizocilpine; Escalation; N-methyl-d-aspartate (NMDA) receptor (NMDAR)