Ballok David A, Szechtman Henry, Sakic Boris
Department of Psychiatry and Behavioural Neurosciences, McMaster University, Main Street West, Hamilton, Ontario, Canada L8N 3Z5.
Behav Brain Res. 2003 Mar 18;140(1-2):119-30. doi: 10.1016/s0166-4328(02)00276-0.
One of the most profound behavioural deficits in lupus-prone MRL-lpr mice is blunted responsiveness to sweet solutions. Given the systemic nature of autoimmune/inflammatory disease, it was not clear whether impaired taste sensitivity or motivated response to palatable food underlie this deficit. The present study compares response rates of MRL-lpr mice (which develop disease early), congenic MRL +/+ mice (which develop disease later in life) and non-autoimmune Swiss Webster (SW) mice to different tastes and diets. Healthy SW mice showed the highest responsiveness to palatable stimulation throughout the study. Conversely, the preference for palatable solutions progressively declined in MRL-lpr mice as the disease developed. No differences between the two MRL substrains were seen in responsiveness to quinine or saline, suggesting that blunted responsiveness to palatable solutions cannot be accounted for by reduced taste sensory function (hypogeusia). In addition, changes in response rates to palatable solutions were associated with systemic upregulation of pro-inflammatory cytokines. With a new cohort of mice fed on carbohydrate-rich and fat-rich diets, we also examined whether reduced sucrose intake in MRL-lpr mice can be accounted for by a reduced craving for carbohydrates. Contrary to this expectation, diseased MRL-lpr mice preferred carbohydrate-rich food while consuming a food mass comparable to controls. These results further support the hypothesis that the onset of lupus-like disease alters motivated behaviour, independent of changes in neurologic function and food metabolism.
易患狼疮的MRL - lpr小鼠最显著的行为缺陷之一是对甜味溶液的反应迟钝。鉴于自身免疫/炎症性疾病的全身性,尚不清楚味觉敏感性受损还是对美味食物的动机反应是导致这种缺陷的原因。本研究比较了MRL - lpr小鼠(早期发病)、同基因MRL +/+小鼠(后期发病)和非自身免疫性瑞士韦伯斯特(SW)小鼠对不同口味和饮食的反应率。在整个研究过程中,健康的SW小鼠对美味刺激表现出最高的反应性。相反,随着疾病的发展,MRL - lpr小鼠对美味溶液的偏好逐渐下降。在对奎宁或盐水的反应性方面,两种MRL亚系之间没有差异,这表明对美味溶液的反应迟钝不能用味觉感觉功能降低(味觉减退)来解释。此外,对美味溶液反应率的变化与促炎细胞因子的全身上调有关。对于一组以富含碳水化合物和富含脂肪的饮食喂养的新小鼠,我们还研究了MRL - lpr小鼠蔗糖摄入量减少是否可以用对碳水化合物的渴望降低来解释。与这种预期相反,患病的MRL - lpr小鼠在消耗与对照组相当的食物量时更喜欢富含碳水化合物的食物。这些结果进一步支持了这样的假设,即狼疮样疾病的发作会改变动机行为,而与神经功能和食物代谢的变化无关。