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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Evaluation of unconditioned novelty-seeking and d-amphetamine-conditioned motivation in mice.
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Evaluation of unconditioned novelty-seeking and d-amphetamine-conditioned motivation in mice.

机译：评估小鼠的无条件新奇寻求和d-苯异丙胺有条件的动机。

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Following repeated association between psychostimulant drugs and a distinct environment, contextual cues acquire the ability to elicit a conditioned approach response. Further, both rats and mice have a natural drive to seek for the experience of novelty, and a previously unknown environment is able to elicit an unconditioned approach response. Both the experience of novelty and amphetamine (AMPH)-conditioned effects have been associated in rodents with the activation of brain meso-limbic dopaminergic pathways. This study assessed the relative strength of AMPH-conditioned and novelty-induced unconditioned motivations in mice. During the pretreatment period, mice were randomly assigned to three different treatment history groups, and received d-AMPH (0, 2, or 10 mg/kg i.p. once/day) injections for 3 days in the presence of a familiar environment. Following a 48-h washout from the last drug injection, animals were placed in the familiar and pretreatment-paired environment and challenged with either SAL (to evaluate conditioning) or a standard AMPH dose (2 mg/kg, to assess either acute drug effects or carryover influences of each animal's treatment history with the same drug). Following the opening of a partition, animals showed both a clear-cut preference for a novel environment as well as a marked novelty-induced hyperactivity. Interestingly, when mice were tested in a drug-free state in this free-choice paradigm, they expressed neither conditioning to the drug-associated environment nor carry-over effects on the novelty-induced hyperactivity profile. On the other hand, mice injected with AMPH showed a mixed profile, with AMPH 2 treatment history mice showing a conditioned preference for the familiar and drug-paired environment, whereas AMPH 10 animals preferred to spend more time in the novel compartment. Both AMPH doses were associated with an increased locomotion, whereas only the AMPH 10 dose resulted in a stereotyped behavioral syndrome, possibly reminiscent of an aversive "poor welfare" condition. Thus, as a function of the drug dosage, differential positive or negative incentive properties are suggested to be evoked by the AMPH-conditioned environment. In conclusion, a reliable and useful experimental paradigm has been developed to investigate the issue of vulnerability to a variety of habit-forming agents or emotional experiences whose positive reinforcing properties may rely on a common neurobiological mechanism.
机译：在精神兴奋药和不同的环境之间反复关联之后，上下文提示获得了引发条件性方法反应的能力。此外，大鼠和小鼠都具有寻求新颖性的自然驱动力，并且先前未知的环境能够引发无条件的进近响应。在啮齿类动物中，新奇经历和苯丙胺（AMPH）调节效应都与大脑中肢多巴胺能途径的激活有关。这项研究评估了AMPH条件小鼠和新奇诱导的条件小鼠的相对强度。在预处理期间，将小鼠随机分为三个不同的治疗史组，并在熟悉的环境中进行d-AMPH（0、2或10 mg / kg腹腔一次/天，每天一次）注射3天。在上次药物注射后48小时冲洗后，将动物置于熟悉且经过预处理的配对环境中，并接受SAL（以评估条件）或标准AMPH剂量（2 mg / kg，以评估急性药物作用）的攻击或相同药物对每只动物治疗史的影响。隔断打开后，动物既表现出对新环境的明显偏好，也表现出明显的新奇诱导的过度活跃。有趣的是，当在这种自由选择范式下以无药物状态测试小鼠时，它们既未表达对药物相关环境的调节，也未表达对新奇诱导的机能亢进特征的影响。另一方面，注射过AMPH的小鼠表现出混合的特征，其中AMPH 2治疗史小鼠表现出对熟悉的和药物配对环境的条件性偏爱，而AMPH 10动物更喜欢在新的隔室中花费更多的时间。两种AMPH剂量都与运动增加有关，而只有AMPH 10剂量会导致刻板的行为综合症，可能使人联想到厌恶的“贫困”状况。因此，根据药物剂量，建议由AMPH调节的环境引起不同的正或负激励特性。总之，已经开发出一种可靠且有用的实验范式来研究对各种习惯形成剂或情绪体验的脆弱性问题，这些习惯形成剂或情绪体验的积极增强特性可能依赖于常见的神经生物学机制。

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