Department of Psychology and Neuroscience, University of Guelph, ON, Canada.
Department of Psychology and Neuroscience, University of Guelph, ON, Canada.
Pharmacol Biochem Behav. 2021 Apr;203:173120. doi: 10.1016/j.pbb.2021.173120. Epub 2021 Jan 23.
Disorders characterized by dysfunction of glucose metabolism are often comorbid with depression. The current study investigated whether a hypoglycemic state caused by 2-deoxy-d-glucose (2-DG) can result in anhedonic behaviors responsive to stimulation of monoamine activity.
In experiment 1, male Sprague-Dawley rats were tested for maintenance of intra-oral self-administration (IOSA) of a sweet solution after pre-treatment with 300 or 500 mg/kg 2-DG, a blocker of glucose metabolism. Experiment 2 determined whether exposure to an environment previously paired with the effects of 2-DG (0, 200 or 300 mg/kg) can influence IOSA, and whether 2-DG can modify taste reactivity to same sweet solution. Finally, experiment 3 examined whether 0 or 30 mg/kg bupropion, a monoamine-reuptake blocker, would attenuate the effect of 300 mg/kg 2-DG on IOSA and taste reactivity.
It was found that 2-DG produced a sustained decrease in IOSA when animals were tested drug-free. This decrease in IOSA did not appear linked to place conditioning or to alterations in taste reactivity, and it was partially normalized by pre-treatment with bupropion.
Taken together, these results in rats suggest that rapid hypoglycemia can induce an anhedonic state characterized by impaired consummatory responses to nutritional incentive stimuli and that can be alleviated by the antidepressant bupropion.
以葡萄糖代谢功能障碍为特征的疾病常与抑郁共病。本研究探讨了 2-脱氧-D-葡萄糖（2-DG）引起的低血糖状态是否会导致对单胺活性刺激有反应的快感缺失行为。
在实验 1 中，雄性 Sprague-Dawley 大鼠在接受 300 或 500mg/kg 2-DG（葡萄糖代谢抑制剂）预处理后，测试其对口腔内自我给药（IOSA）的甜味溶液的维持能力。实验 2 确定了暴露于先前与 2-DG （0、200 或 300mg/kg）作用相关的环境是否会影响 IOSA，以及 2-DG 是否会改变对相同甜味溶液的味觉反应。最后，实验 3 研究了 0 或 30mg/kg 安非他酮（一种单胺再摄取抑制剂）是否会减弱 300mg/kg 2-DG 对 IOSA 和味觉反应的影响。
结果发现，当动物处于无药物状态时，2-DG 会持续降低 IOSA。这种 IOSA 的降低似乎与位置条件作用或味觉反应的改变无关，并且可以通过安非他酮预处理部分恢复正常。
这些在大鼠中的结果表明，快速低血糖可引起快感缺失状态，表现为对营养性激励刺激的消费反应受损，而抗抑郁药安非他酮可缓解这种状态。
