title: Pharmacological and non-pharmacological factors that regulate the acquisition of ketamine self-administration in rats.
abstract: BACKGROUND
  Recreational ketamine use may be modulated by factors such as ketamine infusion patterns, associated conditioned stimuli and spatial-temporal contexts. Our aim was to study the pharmacological and non-pharmacological factors that regulate the acquisition of ketamine use.
  
  
  METHODS
  In experiment 1, four groups of male rats were trained to self-administer ketamine during nine 1-h daily sessions, under four reinforcement schedules: i) pre-session ketamine priming (Priming-[KET]), ii) conditioned stimulus (CS) paired to the ketamine infusions ([KET + CS]), iii) neither priming nor CS ([KET]), iv) combination of both (Priming-[KET + CS]). In experiment 2, two groups of male rats were trained to self-administer ketamine during nine 1-h daily or weekly sessions, under the Priming-[KET + CS] schedule. Lever pressing was then extinguished by saline substitution for ketamine infusion. Afterwards, ketamine was made available again upon responding under the same schedule.
  
  
  RESULTS
  The Priming-[KET + CS] schedule of reinforcement showed a significant increase in the number of ketamine reinforcements and a significant discrimination between active vs. inactive levers. The same schedule allowed the establishment of ketamine self-administration on a weekly basis. During the extinction phase, rate of responding significantly dropped in both weekly and daily groups although it was twofold longer in the former, which showed a lack of reacquisition.
  
  
  CONCLUSIONS
  Both pre-session ketamine priming and a conditioned stimulus paired to the ketamine infusions are required for the acquisition of ketamine self-administration. The longer extinction and the lack of reacquisition in the weekly group could be due to changes in temporal context that might affect the conditioning process.
authors.affiliation: Neuropsychopharmacology Laboratory, Section of Pharmacology, Department of Public Health and Community Medicine, University of Verona, Policlinico Borgo Roma, P.le Scuro 10, 37134, Verona, Italy. venniro.marco@nih.gov.
authors.forename: Marco
authors.initials: M
authors.lastname: Venniro
authors.affiliation: Neuropsychopharmacology Laboratory, Section of Pharmacology, Department of Public Health and Community Medicine, University of Verona, Policlinico Borgo Roma, P.le Scuro 10, 37134, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mutti
authors.affiliation: Neuropsychopharmacology Laboratory, Section of Pharmacology, Department of Public Health and Community Medicine, University of Verona, Policlinico Borgo Roma, P.le Scuro 10, 37134, Verona, Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiamulera
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine
keywords: Conditioned stimulus; Intermittent; Ketamine; Priming; Rat; Reinforcement; Self-administration