Chang Tilly, Meyer Urs, Feldon Joram, Yee Benjamin K
Laboratory of Behavioural Neurobiology, ETH Zurich, Schorenstrasse 16, 8603, Schwerzenbach, Switzerland.
Psychopharmacology (Berl). 2007 Apr;191(2):211-21. doi: 10.1007/s00213-006-0649-z. Epub 2006 Dec 19.
Pre-exposure to either one of the two to-be-associated stimuli alone is known to reduce the efficiency of the learning of their association when they are subsequently paired explicitly. In classical conditioning, pre-exposure to the conditioned stimulus (CS) gives rise to latent inhibition (LI); and pre-exposure to the unconditioned stimulus (US) results in the US pre-exposure effect (USPEE). Considerable evidence supports an important role of central dopamine in the regulation and modulation of LI; it has been suggested that the USPEE may be similarly controlled by dopamine, but this parallelism has only been directly demonstrated in the conditioned taste aversion paradigm.
The present study tested this hypothesis by comparing the efficacy of systemic amphetamine treatment to affect the expression of LI and the USPEE in a two-way active avoidance paradigm.
C57BL/6 male mice were tested in active avoidance using a tone CS and a foot-shock US. Twenty-four hours before, they were pre-exposed to 100 presentations of the CS or the US, or to the test apparatus only. Amphetamine (2.5 mg/kg) or saline was administered before stimulus pre-exposure and conditioned avoidance test, in which the mice learned to avoid the shock by shuttling in response to the tone.
Amphetamine disrupted both stimulus pre-exposure effects, thus, lending further support to the hypothesis that the USPEE is similar to LI in its sensitivity to dopamine receptor agonist. Hence, the USPEE paradigm may represent a valuable addition to the study of dopamine-sensitive processes of selective learning currently implicated in LI and Kamin blocking.
已知单独预先暴露于两种待关联刺激中的任何一种,会降低随后将它们明确配对时其关联学习的效率。在经典条件反射中,预先暴露于条件刺激(CS)会产生潜伏抑制(LI);而预先暴露于非条件刺激(US)会导致非条件刺激预先暴露效应(USPEE)。大量证据支持中枢多巴胺在LI的调节和调制中起重要作用;有人提出USPEE可能同样受多巴胺控制,但这种平行关系仅在条件性味觉厌恶范式中得到直接证明。
本研究通过比较全身性苯丙胺治疗在双向主动回避范式中影响LI和USPEE表达的效果来检验这一假设。
使用音调CS和足部电击US对C57BL/6雄性小鼠进行主动回避测试。在测试前24小时,让它们预先暴露于CS或US的100次呈现中,或者仅暴露于测试装置。在刺激预先暴露和条件回避测试前给予苯丙胺(2.5mg/kg)或生理盐水,在条件回避测试中,小鼠学会通过响应音调穿梭来避免电击。
苯丙胺破坏了两种刺激预先暴露效应,因此,进一步支持了USPEE在对多巴胺受体激动剂的敏感性方面与LI相似的假设。因此,USPEE范式可能是目前与LI和卡明阻断有关的选择性学习的多巴胺敏感过程研究中的一个有价值的补充。