Pharmacological and non-pharmacological factors that regulate the acquisition of ketamine self-administration in rats
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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.
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.
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.
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.
KeywordsKetamine Priming Conditioned stimulus Self-administration Intermittent Reinforcement Rat
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
All animal procedures were carried out in accordance with the Principles of laboratory animal care (NIH publication No. 85-23, revised 1985), the European Communities Council Directive (2010/63/UE). All efforts were made to minimize animal suffering and to use the least animals.
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