Ventral Tegmental Area Cannabinoid Type-1 Receptors Control Voluntary Exercise Performance
Ventral Tegmental Area Cannabinoid Type-1 Receptors Control Voluntary Exercise Performance
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DOI：
10.1016/j.biopsych.2012.10.025
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发表时间：
2013-05-01
影响因子：
10.6
通讯作者：
Chaouloff, Francis
中科院分区：
文献类型：
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作者：
Dubreucq, Sarah;Durand, Audrey;Chaouloff, Francis
背景：我们已经证明，内源性刺激大麻素1型受体(CB1)受体是小鼠自愿跑步的先决条件，但内源性大麻素系统对跑步成绩施加紧张性控制的确切机制尚不清楚。方法：我们分析了结构性/条件性CB1受体突变和CB1受体阻断对车轮跑步成绩的影响。然后，我们评估了腹侧被盖区(VTA)CB1受体阻断对野生型(伽马氨基丁酸[GABA]-CB1+/+)和突变型(GABA-CB1-/-)小鼠大脑GABA神经元CB1受体的影响。结果：GABA-CB1+/+和GABA-CB1-/-小鼠大脑中CB1受体的条件性缺失，而不是其他神经细胞或星形胶质细胞CB1受体的条件性缺失，降低了小鼠的车轮奔跑能力。在GABA-CB1-/-小鼠中，全身或VTA内注射CB1受体拮抗剂对跑步行为的抑制作用被消除。GABA能神经元上CB1受体的缺失导致了急性/重复轮跑后VTA DA神经元活动的抑制。结论：本研究为VTA GABA能神经元上的CB1受体对啮齿动物自主跑步行为的允许控制提供了证据。此外，位于GABA能神经元上的CB1受体可阻止自愿运动对VTA DA神经元活动的负面影响。这些结果表明，内源性大麻素对抑制传递的控制是小鼠车轮运行性能的先决条件。
Background: We have shown that the endogenous stimulation of cannabinoid type-1 (CB1) receptors is a prerequisite for voluntary running in mice, but the precise mechanisms through which the endocannabinoid system exerts a tonic control on running performance remain unknown.Methods: We analyzed the respective impacts of constitutive/conditional CB1 receptor mutations and of CB1 receptor blockade on wheel-running performance. We then assessed the consequences of ventral tegmental area (VTA) CB1 receptor blockade on the wheel-running performances of wildtype (gamma-aminobutyric acid [GABA]-CB1+/+) and mutant (GABA-CB1-/-) mice for CB1 receptors in brain GABA neurons. Using in vivo electrophysiology, the consequences of wheel running on VTA dopamine (DA) neuronal activity were examined in GABA-CB1+/+ and GABA-CB1-/- mice.Results: Conditional deletion of CB1 receptors from brain GABA neurons, but not from several other neuronal populations or from astrocytes, decreased wheel-running performance in mice. The inhibitory consequences of either the systemic or the intra-VTA administration of CB1 receptor antagonists on running behavior were abolished in GABA-CB1-/- mice. The absence of CB1 receptors from GABAergic neurons led to a depression of VTA DA neuronal activity after acute/repeated wheel running.Conclusions: This study provides evidence that CB1 receptors on VTA GABAergic terminals exert a permissive control on rodent voluntary running performance. Furthermore, it is shown that CB1 receptors located on GABAergic neurons impede negative consequences of voluntary exercise on VTA DA neuronal activity. These results position the endocannabinoid control of inhibitory transmission as a prerequisite for wheel-running performance in mice.