Wei Shoupeng, Hertle Sarah, Spanagel Rainer, Bilbao Ainhoa
Behavioral Genetics Research Group, Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Mannheim, 68159, Germany.
Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg University, Mannheim, 68159, Germany.
eNeuro. 2021 May 17;8(3). doi: 10.1523/ENEURO.0029-21.2021. Print 2021 May-Jun.
Glutamatergic input via NMDA and AMPA receptors within the mesolimbic dopamine (DA) pathway plays a critical role in the development of addictive behavior and relapse toward drugs of abuse. Although well-established for drugs of abuse, it is not clear whether glutamate receptors within the mesolimbic system are involved in mediating chronic consumption and relapse following abstinence from a non-drug reward. Here, we evaluated the contribution of mesolimbic glutamate receptors in mediating chronic sugar consumption and the sugar-deprivation effect (SDE), which is used as a measure of relapse-like behavior following abstinence. We studied four inducible mutant mouse lines lacking the GluA1 or GluN1 subunit in either DA transporter (DAT) or D1R-expressing neurons in an automated monitoring system for free-choice sugar drinking in the home cage. Mice lacking either GluA1 or GluN1 in D1R-expressing neurons ( or mice) have altered sugar consumption in both sexes, whereas and do not differ from their respective littermate controls. In terms of relapse-like behavior, female mice show a more pronounced SDE. Given that glutamate receptors within the mesolimbic system play a critical role in mediating relapse behavior of alcohol and other drugs of abuse, it is surprising that these receptors do not mediate the SDE, or in the case of female mice, show an opposing effect. We conclude that a relapse-like phenotype of sugar consumption differs from that of drugs of abuse on the molecular level, at least with respect to the contribution of mesolimbic glutamate receptors.
通过中脑边缘多巴胺（DA）通路中的NMDA和AMPA受体的谷氨酸能输入在成瘾行为的发展以及对滥用药物的复吸中起关键作用。尽管这在滥用药物方面已得到充分证实，但尚不清楚中脑边缘系统中的谷氨酸受体是否参与介导非药物奖励戒断后的慢性消费和复吸。在此，我们评估了中脑边缘谷氨酸受体在介导慢性糖消耗和糖剥夺效应（SDE）中的作用，SDE被用作戒断后类似复吸行为的一种衡量指标。我们在一个用于自由选择在家笼中饮用糖的自动监测系统中，研究了四种在DA转运体（DAT）或表达D1R的神经元中缺乏GluA1或GluN1亚基的诱导型突变小鼠品系。在表达D1R的神经元中缺乏GluA1或GluN1的小鼠（或小鼠）在两性中都有糖消耗的改变，而和与它们各自的同窝对照没有差异。就类似复吸行为而言，雌性小鼠表现出更明显的SDE。鉴于中脑边缘系统中的谷氨酸受体在介导酒精和其他滥用药物的复吸行为中起关键作用，令人惊讶的是这些受体并不介导SDE，或者在雌性小鼠的情况下，表现出相反的作用。我们得出结论，糖消耗的类似复吸表型在分子水平上与滥用药物的表型不同，至少在中脑边缘谷氨酸受体的作用方面是如此。
