Campus P, Accoto A, Maiolati M, Latagliata C, Orsini C
Department of Psychology, University of Rome "Sapienza", Roma, Italy.
Fondazione Santa Lucia IRCSS, European Center for Brain Research, Rome, Italy.
Psychopharmacology (Berl). 2016 Apr;233(7):1157-69. doi: 10.1007/s00213-015-4192-7. Epub 2016 Jan 4.
The expression of sign-tracking (ST) phenotype over goal-tracking (GT) phenotype has been associated to different aspects of impulsive behavior, and depletions of brain serotonin (5-HT) have been shown to selectively increase impulsive action as well as ST.
The present study aimed at testing the relationship between reduced brain 5-HT availability and expression of ST phenotype in a genetic model of individual variation in brain 5-HT functionality. Inbred DBA/2J (DBA) mice are homozygous for the allelic variant of the TPH-2 gene causing lower brain 5-HT function in comparison with C57BL/6J (C57) inbred mice.
Young adult (10 weeks) and adult (14 weeks) C57 and DBA mice were trained in a Pavlovian conditioned approach (PCA) paradigm. Lever-directed (ST) and magazine-directed (GT) responses were measured in 12 daily conditioning sessions. In a second experiment, effect of the medial prefrontal cortex (mPFC) 5-HT depletion by the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) was assessed on acquisition of ST phenotype in adult C57 mice, according to their higher 5-HT functionality compared to DBA mice.
Young adult mice of both strains developed ST phenotype, but only adult DBA mice developed ST phenotype. 5-HT depletion in the mPFC of adult C57 mice completely changed their phenotype, as shown by their increased ST.
These findings indicate that ST phenotype can be the expression of a transitory late developmental stage and that genetic factors determine persistence of this phenotype in adulthood. These findings also support a role of 5-HT transmission in PFC in constraining development of ST phenotype.
与目标追踪（GT）表型相比，信号追踪（ST）表型的表达与冲动行为的不同方面相关，并且已表明脑血清素（5-HT）的消耗会选择性地增加冲动行为以及ST。
本研究旨在测试在脑5-HT功能个体差异的遗传模型中，脑5-HT可用性降低与ST表型表达之间的关系。近交系DBA/2J（DBA）小鼠对于TPH-2基因的等位变体是纯合的，与近交系C57BL/6J（C57）小鼠相比，其脑5-HT功能较低。
将年轻成年（10周）和成年（14周）的C57和DBA小鼠在巴甫洛夫条件性接近（PCA）范式中进行训练。在12次每日条件训练中测量杠杆导向（ST）和食盒导向（GT）反应。在第二个实验中，根据成年C57小鼠与DBA小鼠相比具有更高的5-HT功能，评估了神经毒素5,7-二羟基色胺（5,7-DHT）对成年C57小鼠内侧前额叶皮质（mPFC）5-HT的消耗对ST表型获得的影响。
两个品系的年轻成年小鼠都出现了ST表型，但只有成年DBA小鼠出现了ST表型。成年C57小鼠mPFC中的5-HT消耗完全改变了它们的表型，表现为ST增加。
这些发现表明，ST表型可能是一个短暂的晚期发育阶段的表达，并且遗传因素决定了该表型在成年期的持续性。这些发现还支持PFC中5-HT传递在限制ST表型发展中的作用。
