Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC, Australia; Department of Biochemistry and Pharmacology, University of Melbourne, VIC, Australia; Florey Department of Neuroscience & Mental Health, University of Melbourne, VIC, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, VIC, Australia; Florey Department of Neuroscience & Mental Health, University of Melbourne, VIC, Australia; School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Mar 8;121:110654. doi: 10.1016/j.pnpbp.2022.110654. Epub 2022 Oct 6.
Compulsive overeating of palatable food is thought to underlie some forms of obesity. Similarities are often observed in the behavioural symptomology and the neuropathophysiology underlying substance use disorder and compulsive overeating. As such, preclinical animal models which assess addiction-like behaviour towards food may assist the understanding of the neurobiology underlying overeating behaviour. Further, the relationship between these behaviours and the propensity for diet-induced obesity warrants examination. In this study we investigated the relationship between the propensity for diet-induced obesity (DIO) and addiction-like behaviour towards highly palatable food in C57BL/6 J mice as measured by a 3-criteria model. We also examined the extent to which performance on this 3-criteria model predicted two key hallmark features of addiction - resistance to extinction and relapse propensity (as measured by reinstatement of lever pressing). C57BL/6 J mice were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions whereby addiction-like behaviour towards a high-fat high-sugar food reward was assessed using a 3-criteria model similar to that used to assess addiction-like behaviour towards drugs of abuse. In contrast to findings in rats, no difference in addiction-like behaviour towards food was observed between obesity prone (OP) and obesity resistant (OR) mice. Similarly, principal components analysis found no distinct patterns in the relationship between addiction-like behaviours across treatment groups. This suggests that the strain and species of rodent may be critical for studying the mechanisms underlying pathological overconsumption. Further analysis revealed that the extent of performance on the 3-criteria model correlated with the propensity for C57BL/6 J mice to both extinguish food seeking behaviour and "relapse" after a period of withdrawal. This finding was evident across all groups, regardless of DIO. Collectively, these data validate the 3-criteria model as a robust model to comprehensively assess food addiction-like behaviour in mice, regardless of prior food intake history.
暴食美味食物被认为是某些肥胖形式的基础。在物质使用障碍和强迫性暴食的行为症状学和神经病理生理学基础方面，通常观察到相似之处。因此，评估对食物类似成瘾行为的临床前动物模型可能有助于理解暴饮暴食行为的神经生物学基础。此外，这些行为与饮食诱导肥胖倾向之间的关系值得研究。在这项研究中，我们通过 3 项标准模型评估了 C57BL/6J 小鼠饮食诱导肥胖倾向（DIO）与对高度美味食物类似成瘾行为之间的关系。我们还研究了该 3 项标准模型的表现程度对成瘾的两个关键特征标志的预测程度 - 对消退的抵抗力和复发倾向（通过按压杠杆的恢复来衡量）。C57BL/6J 小鼠在 8 周内自由获得美味饮食，然后根据体重增加分为易肥胖和不易肥胖亚组。然后，美味食物的摄入受到限制，每日操作自我给药会议，使用类似于评估对滥用药物类似成瘾行为的 3 项标准模型评估高脂肪高糖食物奖励的类似成瘾行为。与大鼠的发现相反，在肥胖倾向（OP）和肥胖抵抗（OR）小鼠之间，对食物类似成瘾行为没有差异。同样，主成分分析发现，在治疗组之间，成瘾行为之间没有明显的关系模式。这表明，啮齿动物的品种和物种可能对研究病理性过度消费的机制至关重要。进一步分析表明，3 项标准模型的表现程度与 C57BL/6J 小鼠的两种行为之间的关系相关：一种是食物寻找行为的消退，另一种是在一段时间的戒断后“复发”。这一发现适用于所有群体，与 DIO 无关。总的来说，这些数据验证了 3 项标准模型作为一种全面评估小鼠类似食物成瘾行为的稳健模型，无论先前的食物摄入史如何。
