Evidence supporting the use of glucagon-like peptide-1 (GLP-1) analogues to pharmacologically treat disorders beyond type 2 diabetes and obesity is increasing. However, little is known about how activation of the GLP-1 receptor (GLP-1R) during pregnancy affects maternal and offspring outcomes. We treated female C57Bl/6 J mice prior to conception and throughout gestation with a long-lasting GLP-1R agonist, Exendin-4. While GLP-1R activation has significant effects on food and drug reward, depression, locomotor activity, and cognition in adults, we found few changes in these domains in exendin-4-exposed offspring. Repeated injections of Exendin-4 had minimal effects on the dams and may have enhanced maternal care. Offspring exposed to the drug weighed significantly more than their control counterparts during the preweaning period and demonstrated alterations in anxiety-like outcomes, which indicate a developmental role for GLP-1R modulation in the stress response that may be sex-specific.

支持使用胰高血糖素样肽-1 (GLP-1) 类似物药理学治疗 2 型糖尿病和肥胖症以外疾病的证据正在增加。然而，关于怀孕期间 GLP-1 受体 (GLP-1R) 的激活如何影响母体和后代的结局，我们知之甚少。我们在受孕前和整个妊娠期间用长效 GLP-1R 激动剂 Exendin-4 治疗雌性 C57Bl/6 J 小鼠。虽然 GLP-1R 激活对成人的食物和药物奖励、抑郁、运动活动和认知有显着影响，但我们发现暴露于 exendin-4 的后代在这些领域几乎没有变化。重复注射 Exendin-4 对大坝的影响很小，并且可能增强了母体护理。