title: Interactions of cocaine with dopamine D₂-like antagonists in squirrel monkeys.
abstract: BACKGROUND
  Studies investigating dopamine D₂ receptor antagonism of cocaine's discriminative stimulus effects have resulted in varied effects possibly due to the use of different antagonists, species, and procedures.
  
  
  OBJECTIVE
  The present study sought to further investigate D₂ antagonism of cocaine's discriminative stimulus effects using a variety of D₂ antagonists and multiple doses of the antagonists in combination with cocaine.
  
  
  METHODS
  The benzamide D₂ antagonists, eticlopride, raclopride, and sulpiride, and the butyrophenone D₂ antagonists haloperidol and spiperone were administered alone and in combination with cocaine in squirrel monkeys trained to discriminate cocaine from saline under a fixed-ratio food reinforcement procedure.
  
  
  RESULTS
  All the D₂ antagonists, except haloperidol, antagonized the discriminative stimulus effects of the cocaine training dose. However, only the benzamide D₂ antagonists produced significant rightward shifts in the cocaine discriminative stimulus dose-effect curve and they only did so within a narrow dose range and time after administration. In contrast, the D₂ antagonists failed to antagonize the rate-suppressant effects of cocaine, and in some cases, cocaine appeared to antagonize the rate-suppressant effects of the antagonists.
  
  
  CONCLUSIONS
  The present results suggest (1) that D₂ antagonism of cocaine's discriminative stimulus effects depends critically on the selected antagonist, antagonist dose, and time of administration, as well as how antagonism is assessed (i.e., in terms of effects on training dose or on the cocaine dose-effect curve), (2) that the maximal shift in cocaine's discriminative stimulus dose-effect curve possible with D₂ antagonists under these procedures is ~two- to threefold, and (3) that different effects of cocaine are differentially sensitive to dopamine receptor antagonism.
authors.affiliation: Division of Behavioral Biology, Johns Hopkins University School of Medicine, 5510 Nathan Shock Drive, Suite 3000, Johns Hopkins Bayview Campus, Baltimore, MD 21224-6823, USA. psoto@jhmi.edu
authors.forename: Paul L
authors.initials: PL
authors.lastname: Soto
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Katz
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002090:Butyrophenones / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012453:Saimiri; D013997:Time Factors
chemical_list: D001549:Benzamides; D002090:Butyrophenones; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D003042:Cocaine