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首页> 外文期刊>Addiction biology >Chemogenetic inhibition of direct pathway striatal neurons normalizes pathological, cue-induced reinstatement of drug-seeking in rats
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Chemogenetic inhibition of direct pathway striatal neurons normalizes pathological, cue-induced reinstatement of drug-seeking in rats

机译：直接途径纹状体神经元的化学生成抑制标准化大鼠毒药恢复的病理学，提示急性

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摘要

Addiction to drugs such as cocaine is marked by cycles of compulsive drug-taking and drug-seeking behavior. Although the transition to addiction is thought to recruit neural processes in dorsal striatum, little is known regarding the role of dorsal striatal projections to the substantia nigra (i.e. the direct pathway) in regulating these behaviors. Combining a Cre-recombinase-dependent chemogenetic approach with a cocaine self-administration paradigm that produces both low-risk and high-risk addiction phenotypes, we examined the effect of transiently decreasing direct pathway activity in the dorsomedial striatum on drug-taking and drug-seeking under conditions of normal and pathological drug use. Surprisingly, transient inhibition of direct pathway striatal neurons had no effect on several measures of addictive behavior during ongoing drug use, including loss of control over drug intake, high motivation to obtain drug and drug use despite negative consequences (i.e. drug use paired with foot shock). However, chemogenetic inhibition of these neurons during reinstatement reduced cue-induced drug-seeking, but only in the high-risk addiction phenotype group. Cue-induced reinstatement was relatively normal in the low-risk addiction phenotype group, as well as following reinstatement to cues associated with sucrose pellet consumption. These results demonstrate that dorsomedial direct pathway striatal neurons play a very specific role in addictive behaviors, which is to regulate the pathological drug-seeking that accompanies relapse.
机译：对药物如可卡因等药物的成瘾被强迫药物吸毒和寻求药物行为的循环标记。虽然被认为对成瘾的过渡是招募在背体纹状体中的神经过程，但对背部纹状体突起对规范这些行为的实质性突出物（即直接途径）的作用很少。将Cro-Reobominase依赖性化学性化学方法与可卡因自我管理范例结合起来，产生低风险和高危成瘾表型，我们检查了在药物吸毒和药物中瞬时降低直接途径活性的效果在正常和病理药物使用的条件下寻求。令人惊讶的是，瞬态抑制直接途径纹状体神经元对持续药物使用过程中的几种令人上瘾行为措施没有影响，包括对药物摄入量的丧失，尽管有负面后果（即用足部休克配对的药物使用，但获得药物和吸毒的高动力）。然而，在恢复期间，这些神经元的化学抑制减少了提示诱导的药物寻找，但仅在高危成瘾表型组中。在低风险成瘾表型组中，提示急性恢复相对正常，以及恢复与蔗糖颗粒消耗相关的提示之后。这些结果表明，背侧直接途径纹状体神经元在上瘾行为中发挥着非常具体的作用，这是调节伴随复发的病理毒品。

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