Cannabinoid-induced hyperphagia: Correlation with inhibition of proopiomelanocortin neurons?
Cannabinoid-induced hyperphagia: Correlation with inhibition of proopiomelanocortin neurons?
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DOI：
10.1016/j.physbeh.2007.04.028
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发表时间：
2007-10-22
影响因子：
2.9
通讯作者：
Wagner, Edward J.
中科院分区：
文献类型：
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作者：
Ho, Jennie;Cox, Jeremy M.;Wagner, Edward J.
我们测试了大麻素调节雄性豚鼠摄食的假设，并将大麻素诱导的摄食行为改变与影响下丘脑弓状核原黑素皮质激素（POMC）神经元的谷氨酸能突触电流的改变联系起来。饲养实验如下：在3天的驯化期后，称量动物体重，每天注射cb1受体激动剂WIN 55,212-2 （1 mg/kg, s.c）、拮抗剂AM251 （3 mg/kg, s.c）或其cremophore/乙醇/生理盐水混合剂（1:1:18;1 ml/ kg, s.c），连续7天。WIN 55,212-2增加了累积食物摄取率，而AM251降低了。激动剂的作用主要表现为每餐吃饭次数和食量的增加。相比之下，拮抗剂作用与进餐频率、持续时间和体重减轻有关。在电生理实验中，我们对下丘脑POMC神经元切片进行全细胞膜片钳记录。WIN 55,212-2降低了诱发的谷氨酸能兴奋性突触后电流（eEPSCs）的振幅，增加了S2:S1比值。相反，AM251本身增加了eEPSC振幅，并阻断了激动剂的抑制作用。WIN 55,212-2还降低了微型EPSC （mEPSC）频率；而AM251本身增加了mEPSC频率，并再次阻断了激动剂的抑制作用。细胞亚群表现出激动剂诱导的向外电流，该电流被AM251阻断，与K+的电导增加和能量平衡电位附近的极性逆转有关。这些数据表明，大麻素在一定程度上通过对厌氧性POMC神经元的突触前和突触后作用来调节豚鼠的食欲。((c)。2007爱思唯尔公司版权所有。
We tested the hypothesis that cannabinoids modulate feeding in male guinea pigs, and correlated cannabinoid-induced changes in feeding behavior with alterations in glutamatergic synaptic currents impinging upon proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus. Feeding experiments were performed as follows: after a three-day acclimation period, animals were weighed and injected with either the CB 1 receptor agonist WIN 55,212-2 (1 mg/kg, s.c.), antagonist AM251 (3 mg/kg, s.c.) or their cremophore/ethanol/saline vehicle (1: 1: 18; 1 ml/ kg, s.c.) each day for seven days. WIN 55,212-2 increased, whereas AM251 decreased, the rate of cumulative food intake. The agonist effect was manifest primarily by increases in meal frequency and the amount of food eaten per meal. By contrast, the antagonist effect was associated with decreases in meal frequency, duration and weight loss. For the electrophysiological experiments, we performed whole-cell patch-clamp recordings from POMC neurons in hypothalamic slices. WIN 55,212-2 decreased the amplitude of evoked, glutamatergic excitatory postsynaptic currents (eEPSCs) and increased the S2:S1 ratio. Conversely, AM251 increased eEPSC amplitude per se, and blocked the inhibitory effects of the agonist. WIN 55,212-2 also decreased miniature EPSC (mEPSC) frequency; whereas AM251 increased mEPSC frequency per se, and again blocked the inhibitory effect of the agonist. A subpopulation of cells exhibited an agonist-induced outward current, which was blocked by AM251, associated with increased conductance and reversed polarity near the Nernst equilibrium potential for K+. These data demonstrate that cannabinoids regulate appetite in the guinea pig in part through both presynaptic and postsynaptic actions on anorexigenic POMC neurons. ((c) .2007 Elsevier Inc. All rights reserved.