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重新审视大鼠长时程与短时程可卡因自我给药:间歇性摄入促进成瘾症状出现,与给药时长无关。

Revisiting long-access versus short-access cocaine self-administration in rats: intermittent intake promotes addiction symptoms independent of session length.

机构信息

Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Canada.

CNS Research Group, Faculty of Medicine, Université de Montréal, Canada.

出版信息

Addict Biol. 2019 Jul;24(4):641-651. doi: 10.1111/adb.12629. Epub 2018 Jun 19.

Abstract

In rats, continuous cocaine access during long self-administration sessions (6 versus 1-2 hours) promotes the development of behavioral symptoms of addiction. This has led to the assumption that taking large amounts of drug during extended daily bouts is necessary to develop an addiction phenotype. Recent work shows that within-session intermittent access (IntA) to cocaine produces much less drug intake than continuous-access procedures (i.e. long-access sessions) but evokes addiction symptoms more effectively. IntA-sessions are also long, typically lasting 6 hours. It is not known whether IntA-sessions must be extended to promote addiction-relevant changes in drug use over time. Here, we determined the influence of IntA-session length on patterns of cocaine use relevant to addiction. Two groups of male Wistar rats self-administered cocaine (0.25 mg/kg/injection, injected over 5 seconds) during 18 daily IntA-sessions. One group had long 6-hour sessions (Long-IntA), the other group had shorter, 2-hour sessions (Short-IntA). Only Long-IntA rats escalated their cocaine intake over sessions, but both groups developed a burst-like pattern of drug use over time and similar levels of psychomotor sensitization. The two groups also showed robust and similar levels of both responding for cocaine under a progressive ratio schedule of reinforcement and cocaine-induced reinstatement of extinguished drug-seeking behavior. In summary, long IntA-sessions lead to greater cocaine intake than shorter IntA-sessions, but the two conditions are equally effective in evoking the patterns of drug-taking and drug-seeking that define addiction. This suggests that chronic intermittent cocaine use, even during short daily bouts, is sufficient to promote addiction symptoms.

摘要

在大鼠中,长时间(6 小时而非 1-2 小时)的连续可卡因自我给药会促进成瘾行为症状的发展。这导致了一种假设,即延长每日发作期间摄入大量药物是发展成瘾表型所必需的。最近的研究表明,在单次给药期间进行间歇性给药(IntA)比连续给药程序(即长时间给药)产生的药物摄入量要少得多,但更有效地引起成瘾症状。IntA 给药时间也很长,通常持续 6 小时。目前尚不清楚 IntA 给药时间是否必须延长才能随着时间的推移促进与药物使用相关的成瘾相关变化。在这里,我们确定了 IntA 给药时间长度对与成瘾相关的可卡因使用模式的影响。两组雄性 Wistar 大鼠在 18 天的每日 IntA 给药期间自我给药(0.25mg/kg/注射,5 秒内注射)。一组接受长 6 小时的 IntA 给药(长 IntA),另一组接受短 2 小时的 IntA 给药(短 IntA)。只有长 IntA 组在给药期间增加可卡因摄入量,但两组在时间上都发展出爆发式的药物使用模式,并且出现相似水平的运动敏化。两组也表现出可卡因强化递增比率程序下可卡因反应和可卡因诱导的已熄灭觅药行为恢复的强烈且相似的水平。总之,长 IntA 给药导致可卡因摄入量大于短 IntA 给药,但两种条件在引发定义成瘾的药物使用和觅药模式方面同样有效。这表明慢性间歇性可卡因使用,即使在短时间内,也足以促进成瘾症状。

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