Department of Exercise Physiology, Beijing Sport University, Beijing, 100084, China.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA.
Sci Rep. 2017 Nov 15;7(1):15657. doi: 10.1038/s41598-017-16034-9.
Resveratrol is a natural phytoalexin synthesized by plants, including grapes. It displays a wide range of neuroprotective benefits associated with anti-aging. Recent studies have shown that resveratrol regulates dopaminergic transmission and behavioral effects of drugs of abuse. The goal of the present study is to investigate whether and how resveratrol alters basal inhibitory synaptic transmission and cocaine-induced inhibitory synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA). We report that resveratrol elevated cAMP levels by itself and further potentiated a forskolin-induced increase in cAMP levels in midbrain slices, consistent with reported effects of inhibition of phosphodiesterases (PDEs). Resveratrol potentiated GABA and GABA-mediated inhibitory postsynaptic currents (IPSCs) in VTA dopamine neurons, and these effects were mediated by a protein kinase A (PKA)-dependent enhancement of presynaptic GABA release. In addition, we found that resveratrol blocked endocannabinoid-mediated long-term synaptic depression in VTA dopamine neurons. Resveratrol pretreatments attenuated cocaine-induced conditioned place preference and blocked the cocaine-induced reduction of GABAergic inhibition in VTA dopamine neurons. Together, these results provide evidence that resveratrol modulates basal inhibitory synaptic transmission, cocaine-induced synaptic plasticity, and drug-cue associative learning.
白藜芦醇是一种植物（包括葡萄）合成的天然植物抗毒素，具有广泛的神经保护作用，与抗衰老有关。最近的研究表明，白藜芦醇调节多巴胺能递质传递和滥用药物的行为效应。本研究的目的是探讨白藜芦醇是否以及如何改变腹侧被盖区（VTA）多巴胺神经元的基础抑制性突触传递和可卡因诱导的抑制性突触可塑性。我们报告说白藜芦醇本身就能升高 cAMP 水平，并进一步增强了中脑切片中 forskolin 诱导的 cAMP 水平升高，这与磷酸二酯酶（PDEs）抑制的报道作用一致。白藜芦醇增强了 VTA 多巴胺神经元中的 GABA 和 GABA 介导的抑制性突触后电流（IPSCs），这些作用是通过蛋白激酶 A（PKA）依赖性增强突触前 GABA 释放来介导的。此外，我们发现白藜芦醇阻断了 VTA 多巴胺神经元中内源性大麻素介导的长时程突触抑制。白藜芦醇预处理可减弱可卡因诱导的条件性位置偏好，并阻断可卡因诱导的 VTA 多巴胺神经元中 GABA 能抑制的减少。总之，这些结果提供了证据表明，白藜芦醇调节基础抑制性突触传递、可卡因诱导的突触可塑性和药物线索联想学习。
