Rationale

Cocaine addiction is a global health problem with no approved pharmacotherapies. Preclinical research indicates the non-intoxicating phytocannabinoid, cannabidiol (CBD), can reduce addiction-relevant behaviour for several drug classes (e.g. ethanol, opiates, psychostimulants) in rodents. However, research into the effects of CBD on cocaine addiction-like behaviours is limited, and the acute effects of CBD on cocaine reward are unknown.

Objectives

The present experiments sought to clarify the effects of CBD (10 mg/kg) on the acquisition, consolidation, reconsolidation, extinction and drug-primed reinstatement of cocaine (15 mg/kg) conditioned place preference (CPP) in adult male C57BL6/J mice.

Methods

In five separate experiments, CBD was administered 1) prior to cocaine-context pairings, to target acquisition of cocaine-context memory; 2) immediately after cocaine-context pairings, to target consolidation of cocaine-context memory; 3) after a brief reactivation session, to target reconsolidation of cocaine memory; 4) prior to extinction sessions; and 5) prior to cocaine-primed reinstatement.

Results

CBD treatment reduced preference for the cocaine-context 20 days after CBD cessation. CBD also reduced consolidation of cocaine memory, and this was evident 1 day after cessation of CBD treatment. Interestingly, CBD treatment also modified cocaine-induced locomotion. CBD did not affect reconsolidation of cocaine-induced place preference, the rate of extinction of cocaine memory, or drug-primed reinstatement of cocaine CPP.

Conclusions

These findings indicate specific effects of acute 10 mg/kg CBD on cocaine memory processes, suggesting delayed effects on cocaine preference and consolidation of cocaine memory, and support the therapeutic utility of CBD for targeting some drug-associated memory processes.

中文翻译：

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卡纳比多醇（CBD）减少小鼠中的可卡因环境记忆

基本原理

可卡因成瘾是全球性的健康问题，没有经过批准的药物治疗。临床前研究表明，无毒的植物大麻素大麻二酚（CBD）可以减少啮齿动物中几种药物类别（例如乙醇，阿片类药物，精神兴奋剂）的成瘾相关行为。然而，关于CBD对可卡因成瘾样行为的影响的研究是有限的，CBD对可卡因报酬的急性影响尚不清楚。

目标

本实验试图阐明CBD（10 mg / kg）对成年雄性C57BL6 / J可卡因（15 mg / kg）条件性位置偏爱（CPP）的获得，巩固，再巩固，消灭和药物引发的恢复作用老鼠。

方法

在五个独立的实验中，对CBD进行了管理：1）在可卡因语境配对之前，以获取可卡因语境记忆为目标；2）在可卡因语境配对之后，以巩固可卡因语境记忆为目标；3）在短暂的重新激活会话之后，以可卡因记忆的重新整合为目标；4）在灭绝会议之前；5）可卡因引发的恢复之前。

结果

CBD治疗在CBD停止后20天降低了对可卡因背景的偏好。CBD还减少了可卡因记忆的巩固，这在停止CBD治疗后1天就很明显。有趣的是，CBD治疗还改变了可卡因诱导的运动。CBD不会影响可卡因诱导的位置偏好的重新整合，可卡因记忆的消失率或药物引发的可卡因CPP的恢复。

结论

这些发现表明急性10 mg / kg CBD对可卡因记忆过程的特定作用，提示对可卡因偏爱和可卡因记忆巩固的延迟作用，并支持CBD用于靶向某些与药物相关的记忆过程。