Abstract

Background and purpose

The use of the recreational drug gamma-hydroxybutyric acid (GHB) has increased over the past decade, concomitantly leading to a higher incidence of GHB use disorder. Evidence-based treatment interventions are hardly available and cognitive effects of long-term GHB use remain elusive. In order to study the development of GUD and the causal effects of chronic GHB consumption, a GHB self-administration model is required.

Experimental approach

Long Evans rats had access to GHB in their home cage according to a two-bottle choice procedure for 3 months. Intoxication and withdrawal symptoms were assessed using an automated sensor-based setup for longitudinal behavioral monitoring. Rats were trained in an operant environment according to a fixed ratio (FR) 1, 2, and 4 schedule of reinforcement. Addiction-like behaviors were assessed through progressive ratio-, non-reinforced-, and quinine-adulterated operant tests. In addition, the novel object recognition test and elevated plus maze test were performed before and after GHB self-administration to assess memory performance and anxiety-like behavior, respectively.

Key results

All rats consumed pharmacologically relevant levels of GHB in their home cage, and their intake remained stable over a period of 3 months. No clear withdrawal symptoms were observed following abstinence. Responding under operant conditions was characterized by strong inter-individual differences, where only a subset of rats showed high motivation for GHB, habitual GHB-seeking, and/or continued responding for GHB despite an aversive taste. Male rats showed a reduction in long-term memory performance 3 months after home-cage GHB self-administration. Anxiety-like behavior was not affected by GHB self-administration.

Conclusion and implications

The GHB self-administration model was able to reflect individual susceptibility for addiction-like behavior. The reduction in long-term memory performance upon GHB self-administration calls for further research into the cognitive effects of chronic GHB use in humans.

中文翻译：

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近交系大鼠新自愿 GHB 自我给药模型中 GHB 消耗的个体差异

摘要

背景和目的

过去十年中，娱乐性药物 γ-羟基丁酸 (GHB) 的使用有所增加，同时导致 GHB 使用障碍的发生率更高。几乎没有循证治疗干预措施，长期使用 GHB 对认知的影响仍然难以捉摸。为了研究 GUD 的发展和慢性 GHB 消耗的因果影响，需要 GHB​​ 自我给药模型。

实验方法

Long Evans 大鼠可以根据两瓶选择程序在其家中笼子中使用 GHB，为期 3 个月。使用基于传感器的自动纵向行为监测装置评估中毒和戒断症状。根据固定比率 (FR) 1、2 和 4 强化计划在操作环境中对大鼠进行训练。通过渐进比率、非强化和奎宁掺假操作测试来评估成瘾样行为。此外，在GHB自我给药前后进行新物体识别测试和高架十字迷宫测试，分别评估记忆表现和焦虑样行为。

主要成果

所有大鼠在其饲养笼中消耗了药理学相关水平的 GHB，并且其摄入量在 3 个月内保持稳定。戒断后没有观察到明显的戒断症状。在操作条件下的反应具有强烈的个体间差异的特点，其中只有一部分大鼠表现出对 GHB 的高度动机、习惯性的 GHB 寻求和/或尽管有厌恶的味道但仍继续对 GHB 做出反应。雄性大鼠在家笼自我施用 GHB 3 个月后，表现出长期记忆能力下降。焦虑样行为不受 GHB 自我给药的影响。

结论和启示

GHB 自我给药模型能够反映个体对成瘾样行为的易感性。自我施用 GHB 会导致长期记忆能力下降，因此需要进一步研究长期使用 GHB 对人类认知的影响。