Department of Symptom Research, The University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX, 77030, USA.
Neurobiotechnology Research Group, Federal University of Pelotas, Pelotas, Rio Grande do Sul, 96160-000, Brazil.
Psychopharmacology (Berl). 2021 Mar;238(3):691-697. doi: 10.1007/s00213-020-05721-7. Epub 2021 Jan 7.
Reduced motivation is one of the main symptomatic features of inflammation-induced depression. However, the exact nature of inflammation-induced alterations in motivation remains to be fully defined. As inflammation has been shown to increase sensitivity to negative stimuli, the present series of experiments was initiated to determine whether systemic inflammation induced by infra-septic doses of lipopolysaccharide (LPS) in mice influences consummatory and instrumental responding to successive negative contrast.
Successive negative contrast was operationally defined by a shift to a lower value reward than the one mice were trained with. Mice were trained to drink a high sucrose concentration solution and exposed to an acute shift to a lower concentration of sucrose. In another series of experiments, mice were trained to nose poke for chocolate pellets according to a fixed reinforcement schedule 10 (10 nose pokes for the food reinforcement) and exposed to a shift to a lower reward value (decreased number of chocolate pellets or replacement of chocolate pellets by less preferred grain pellets). Lipopolysaccharide (LPS) was administered at the dose of 0.33 1 mg/kg 24 h before the shift.
Mice trained to drink a high sucrose concentration responded to the shift in reward value by a reduction in the volume of sucrose consumed and a decrease in lick numbers and bout durations. Mice trained to nose poke for chocolate pellets responded to the shift by alterations in their total number of nose pokes. In both conditions, LPS had no consistent effect on the response to the shift in reward value.
These findings indicate a high variability in the effects of LPS on successive negative contrast and fail to provide evidence in favor of the hypothesis that LPS increases sensitivity to decreases in expected rewards.
动机降低是炎症引起的抑郁的主要症状特征之一。然而，炎症引起的动机改变的确切性质仍有待充分定义。由于炎症已被证明会增加对负面刺激的敏感性，因此本系列实验旨在确定在小鼠中由亚致死剂量的脂多糖（LPS）引起的全身性炎症是否会影响连续负对比的消费和工具反应。
连续负对比通过比小鼠接受训练的奖励值低的奖励值转变来操作定义。小鼠接受高蔗糖浓度溶液的训练，并暴露于蔗糖浓度突然降低的情况。在另一系列实验中，根据固定的强化时间表 10（10 次鼻刺获得食物强化）训练小鼠进行巧克力丸鼻刺，并暴露于奖励值降低的情况（巧克力丸数量减少或用不太喜欢的谷物丸代替巧克力丸）。LPS 在转变前 24 小时以 0.33 1 毫克/千克的剂量给药。
接受高蔗糖浓度训练的小鼠对奖励值的转变做出了反应，表现为消耗的蔗糖量减少，舔次数和发作持续时间减少。接受巧克力丸鼻刺训练的小鼠对转变做出了反应，表现为总鼻刺次数的改变。在这两种情况下，LPS 对奖励值转变的反应均无一致影响。
这些发现表明 LPS 对连续负对比的影响具有高度的可变性，并且没有证据支持 LPS 增加对预期奖励减少的敏感性的假设。
