Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, USA.
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Pharmacology, University of Michigan, Ann Arbor, MI, 48109, USA.
Behav Brain Res. 2020 Feb 17;380:112318. doi: 10.1016/j.bbr.2019.112318. Epub 2019 Nov 21.
Continually rising global obesity rates present a major challenge to human health. The contribution of Pavlovian motivational processes to overeating and obesity has become increasingly apparent. In humans, brain and behavioral reactivity to food-related stimuli positively correlates with subsequent weight gain. In concordance with this, selectively bred obesity-prone rats show stronger single-outcome Pavlovian-to-instrumental transfer (SO PIT) than obesity-resistant rats, providing support for the hypothesis that enhanced Pavlovian motivation is a pre-existing phenotype of obesity-susceptibility. However, whether obesity-susceptibility in outbred rats is associated with similar enhancements in PIT was unknown. Moreover, given that SO PIT does not distinguish between sensory specific and general affective motivational processes, it was unclear which of these was linked to obesity-susceptibility. Thus, here we determined whether obesity-susceptibility is associated with enhanced Sensory Specific (SS) PIT versus General PIT using both outbred and selectively bred populations. Rats were trained with two action-outcome and three stimulus-outcome associations; two of the Pavlovian and instrumental associations shared a common outcome. During PIT testing, the influence of the Pavlovian stimuli on the two instrumental responses were measured simultaneously. In outbred rats, expression of General PIT was positively correlated with subsequently determined obesity-susceptibility. In selectively bred rats, General PIT was stronger in obesity-prone versus obesity-resistant rats. Jointly, these data show that enhanced affective Pavlovian motivation is tightly linked to obesity vulnerability, supporting a role for phenotypic differences in incentive motivation in vulnerability to obesity. This has important implications for obesity prevention and for the specific neurocircuitry underlying enhanced food-seeking in vulnerable populations.
不断上升的全球肥胖率对人类健康构成了重大挑战。巴甫洛夫动机过程对暴饮暴食和肥胖的贡献变得越来越明显。在人类中，大脑和行为对与食物相关的刺激的反应与随后的体重增加呈正相关。与此一致的是，选择性繁殖的肥胖易感大鼠比肥胖抵抗大鼠表现出更强的单一结果巴甫洛夫到工具性转移（SO PIT），为增强的巴甫洛夫动机是肥胖易感性的预先存在的表型这一假设提供了支持。然而，在外源性大鼠中，肥胖易感性是否与类似的 PIT 增强有关尚不清楚。此外，由于 SO PIT 不能区分感觉特异性和一般情感动机过程，因此不清楚哪一个与肥胖易感性有关。因此，在这里，我们使用外源性和选择性繁殖的种群来确定肥胖易感性是否与增强的感觉特异性（SS）PIT 与一般 PIT 有关。大鼠接受两种动作-结果和三种刺激-结果关联的训练；两个巴甫洛夫和工具关联具有共同的结果。在 PIT 测试期间，同时测量了巴甫洛夫刺激对两个工具反应的影响。在外源性大鼠中，一般 PIT 的表达与随后确定的肥胖易感性呈正相关。在选择性繁殖的大鼠中，肥胖易感大鼠的一般 PIT 强于肥胖抵抗大鼠。总的来说，这些数据表明，增强的情感性巴甫洛夫动机与肥胖易感性密切相关，支持激励动机表型差异在肥胖易感性中的作用。这对肥胖预防以及脆弱人群中增强的食物寻求的特定神经回路具有重要意义。
