Clinical, Educational and Health Psychology, University College London, Gower Street, London, WC1E 6BT.
University College Hospital and University College Hospital at Westmoreland Street, London, UK.
Psychol Med. 2021 Jan;51(1):158-167. doi: 10.1017/S003329171900312X. Epub 2019 Nov 18.
Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation.
Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up.
Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices.
We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.
将环境食物线索与高美味食物奖励联系起来的适应性学习在肥胖和暴食障碍中过度进食行为中起着核心作用。记忆再巩固的过程提供了一种削弱这种学习的机制，可能会改善过度进食行为。在这里，我们研究了使用雷帕霉素（mTOR）抑制剂雷帕霉素是否通过阻断再巩固来削弱检索到的巧克力奖励记忆，从而潜在地干扰突触可塑性。
75 名有暴食巧克力倾向的健康志愿者被随机分为在 10mg 雷帕霉素（RET + RAP，活性条件）或安慰剂（RET + PBO）下检索巧克力奖励记忆，或在无后续检索的情况下接受 10mg 雷帕霉素（NO RET + RAP）。在操作前一周和操作后一周以及一个月随访时评估巧克力奖励记忆强度的指标。
与假设相反，RET + RAP 组在巧克力线索的动机显著性、巧克力消费动机或巧克力喜好的指标上并没有比对照组表现出更大的降低。在 RET + RAP 组中发现了一些改善的微弱证据，但这仅限于减少巧克力暴食发作和改善健康食品选择。
我们没有发现雷帕霉素能全面阻断自然巧克力奖励记忆再巩固的令人信服的证据。对巧克力暴食和食物选择的影响可能需要进一步研究。这些有限的积极发现可能归因于 10mg 雷帕霉素对 mTOR 信号的干扰不足，或者在检索过程中未能使巧克力记忆不稳定。
