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在大鼠可卡因自我给药戒断期间,不同的饲养条件引起多巴胺 D 样和代谢型谷氨酸受体 5 密度的改变。

Alternation in dopamine D-like and metabotropic glutamate type 5 receptor density caused by differing housing conditions during abstinence from cocaine self-administration in rats.

机构信息

1 Department of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.

2 Department of Toxicology, Faculty of Pharmacy, Jagiellonian University Collegium Medicum, Kraków, Poland.

出版信息

J Psychopharmacol. 2019 Mar;33(3):372-382. doi: 10.1177/0269881118821113. Epub 2019 Jan 15.

Abstract

BACKGROUND

Environmental conditions have an important function in substance use disorder, increasing or decreasing the risks of relapse. Several studies strongly support the role of the dopamine D-like and metabotropic glutamate type 5 receptors in maladaptive neurobiological responses to cocaine reward and relapse.

AIMS

The present study employed cocaine self-administration with yoked-triad procedure in rats to explore whether drug abstinence in different housing conditions affects the drug-seeking behaviour and the dopamine D-like and metabotropic glutamate type 5 receptor density and affinity in several regions of the animal brain.

METHODS

Rats were trained to self-administer cocaine and later they were forced to abstain either in: (a) enriched environment or (b) isolation cage conditions to evaluate the effect of housing conditions on the drug-seeking behaviour and to assess changes concerning receptors in animals brain.

RESULTS

Our results show that exposure to enriched environment conditions strongly reduced active lever presses during cue-induced drug-seeking. At the neurochemical level, we demonstrated a significant increase in the dopamine D-like receptor density in the prefrontal cortex in animals following drug abstinence in isolation cage or enriched environment conditions, and the reduction in their density in the dorsal striatum provoked by isolation cage conditions. The metabotropic glutamate type 5 receptor density decreased only in the prefrontal cortex after isolation cage and enriched environment abstinence.

CONCLUSIONS

This study shows the different impacts caused by the type of housing conditions during abstinence from cocaine self-administration on drug-seeking behaviour in rats. The observed changes in the dopamine D-like and metabotropic glutamate type 5 receptor B and/or K values were brain-region specific and related to either pharmacological and/or motivational features of cocaine.

摘要

背景

环境条件在物质使用障碍中起着重要作用,增加或降低复发的风险。几项研究强烈支持多巴胺 D 样和代谢型谷氨酸 5 型受体在可卡因奖赏和复吸的适应不良神经生物学反应中的作用。

目的

本研究采用大鼠可卡因自我给药与对偶三联程序,探讨不同的戒毒环境是否会影响觅药行为以及动物大脑中几个区域的多巴胺 D 样和代谢型谷氨酸 5 型受体密度和亲和力。

方法

大鼠被训练自我给予可卡因,然后被强制在以下两种环境中戒毒:(a)丰富环境或(b)隔离笼环境,以评估环境条件对觅药行为的影响,并评估动物大脑中受体的变化。

结果

我们的结果表明,暴露在丰富的环境条件下,强烈减少了线索诱导的觅药行为中的主动杠杆按压次数。在神经化学水平上,我们证明了在隔离笼或丰富环境戒毒后,动物前额皮质中的多巴胺 D 样受体密度显著增加,而在隔离笼条件下,背侧纹状体中的受体密度减少。只有在隔离笼和丰富环境戒毒后,前额皮质中的代谢型谷氨酸 5 型受体密度才会降低。

结论

这项研究表明,在可卡因自我给药戒毒期间,不同类型的戒毒环境对大鼠觅药行为产生不同的影响。观察到的多巴胺 D 样和代谢型谷氨酸 5 型受体 B 和/或 K 值的变化是特定于脑区的,与可卡因的药理学和/或动机特征有关。

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