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青春期大鼠对乙醇诱导的慢性耐受性发展和乙醇诱导的条件性厌恶具有抗性。

Adolescent rats are resistant to the development of ethanol-induced chronic tolerance and ethanol-induced conditioned aversion.

作者信息

Pautassi Ricardo Marcos, Godoy Juan Carlos, Molina Juan Carlos

机构信息

Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET - Universidad Nacional de Córdoba), Córdoba C.P 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba C.P 5000, Argentina.

Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba C.P 5000, Argentina.

出版信息

Pharmacol Biochem Behav. 2015 Nov;138:58-69. doi: 10.1016/j.pbb.2015.09.012. Epub 2015 Sep 18.

Abstract

The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake.

摘要

对成年和青少年大鼠乙醇慢性耐受性的分析得出了复杂的结果。有研究报道青少年对乙醇的某些作用存在耐受性,但其他研究发现成年人比青少年表现出更高的耐受性,或者两个年龄段对该现象的表达相当。另一个未得到解答的问题是,慢性乙醇暴露如何影响这些年龄段后续乙醇介导的动机性学习。本研究检测了雄性Wistar成年和青少年大鼠隔天经胃内给予乙醇后,对乙醇低温和运动刺激作用的慢性耐受性发展情况,以及随后对乙醇介导的气味条件反射的习得情况。在诱导期,成年和青少年大鼠对乙醇的低温作用均缺乏耐受性;而在激发期成年大鼠(而非青少年大鼠)的体温降低有下降趋势(实验1)。与成年大鼠不同,青少年大鼠在首次给予乙醇后出现乙醇诱导的运动激活。成年大鼠(而非青少年大鼠)表现出对乙醇的条件性气味厌恶。后续仅在青少年大鼠中进行的实验(实验2、实验3和实验4)对乙醇给药的环境、时长和可预测性进行了操控。这些操控并未促进乙醇诱导耐受性的表达。本研究表明,当每隔一天给予中等剂量乙醇并持续相对较短时间时,青少年大鼠比成年大鼠更不容易对乙醇诱导的低温产生慢性耐受性。这种对耐受性发展的抗性可能会限制乙醇摄入量的长期维持。然而,青少年大鼠比成年大鼠对乙醇的急性运动刺激作用更敏感,但对乙醇厌恶作用的反应减弱。这种反应模式可能使青少年大鼠面临早期开始摄入乙醇的风险

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