Venniro Marco, Mutti Anna, Chiamulera Cristiano
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.
Psychopharmacology (Berl). 2015 Dec;232(24):4505-14. doi: 10.1007/s00213-015-4077-9. Epub 2015 Sep 21.
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.
娱乐性氯胺酮使用可能受氯胺酮输注模式、相关条件刺激和时空背景等因素调节。我们的目的是研究调节氯胺酮使用习得的药理学和非药理学因素。
在实验1中，四组雄性大鼠在每天9个1小时的时段内接受训练，以自我给药氯胺酮，采用四种强化程序：i）时段前氯胺酮启动（启动-[氯胺酮]），ii）与氯胺酮输注配对的条件刺激（[氯胺酮+条件刺激]），iii）既无启动也无条件刺激（[氯胺酮]），iv）两者结合（启动-[氯胺酮+条件刺激]）。在实验2中，两组雄性大鼠在每天或每周9个1小时的时段内接受训练，以自我给药氯胺酮，采用启动-[氯胺酮+条件刺激]程序。然后通过用盐水替代氯胺酮输注来消除杠杆按压行为。之后，在相同程序下做出反应时，氯胺酮再次可用。
启动-[氯胺酮+条件刺激]强化程序显示氯胺酮强化次数显著增加，且主动杠杆与非主动杠杆之间有显著区分。相同程序允许在每周基础上建立氯胺酮自我给药行为。在消退阶段，每周组和每日组的反应率均显著下降，尽管前者下降时间长两倍，且未显示重新习得现象。
氯胺酮自我给药的习得需要时段前氯胺酮启动以及与氯胺酮输注配对的条件刺激。每周组更长的消退时间和缺乏重新习得现象可能是由于时间背景变化可能影响条件作用过程所致。
