Induction of hyperphagia and carbohydrate intake by μ-opioid receptor stimulation in circumscribed regions of frontal cortex.
Induction of hyperphagia and carbohydrate intake by μ-opioid receptor stimulation in circumscribed regions of frontal cortex.
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DOI：
10.1523/jneurosci.2050-10.2011
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发表时间：
2011-03-02
期刊：
影响因子：
--
通讯作者：
Baldo BA
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文献类型：
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作者：
Mena JD;Sadeghian K;Baldo BA
额叶皮质区域被食物相关的刺激激活，这种激活在饮食障碍患者中似乎是失调的。然而，对基本的无条件摄食反应的正面控制仍然知之甚少。在这里，我们发现μ阿片受体刺激可以在腹侧前额叶皮质(VmPFC)和眶前叶皮质的受限区域驱动吞噬功能亢进。在随意喂养和限食的雄性SD大鼠中，双侧输注μ阿片激动剂DAMGO显著增加了标准大鼠食物的摄入量。当在美味的脂肪和碳水化合物丰富的试验饮食之间进行选择时，vmPFC DAMGO内输液选择性地增加碳水化合物的摄入量，即使是在有基线脂肪偏好的大鼠中也是如此。大鼠也表现出运动多动，其特征是在短暂的研究行为和摄食行为之间快速切换。注射vmPFC DAMGO既不影响饮水量，也不影响非特异性口腔行为。将类似的DAMGO注入眼眶外侧或前运动皮质的邻近区域，对进食的影响微乎其微。既不刺激vmPFC定位的β-阿片、kappa-阿片、多巴胺、5-羟色胺或去甲肾上腺素能受体，也不拮抗D_1、5HT1a、α或β-肾上腺素能受体，都不能复制DAMGO效应的轮廓。蝇草醇介导的vmPFC失活，以及vmPFC内刺激κ-阿片受体或阻断5HT2A受体，抑制了运动活动和延长了摄食持续时间-与DAMGO的情况相反。因此，μ-阿片类药物诱导的过度吞噬和碳水化合物摄入可以从额叶皮质的不同亚区引起，具有显著的药理和行为特异性。这些发现可能对理解情感驱动的进食和饮食紊乱中的克制丧失有意义。
Frontal cortical regions are activated by food-associated stimuli, and this activation appears to be dysregulated in individuals with eating disorders. Nevertheless, frontal control of basic unconditioned feeding responses remains poorly understood. Here we show that hyperphagia can be driven by μ-opioid receptor stimulation in restricted regions of ventral medial prefrontal cortex (vmPFC) and orbitofrontal cortex. In both ad libitum-fed and food-restricted male Sprague-Dawley rats, bilateral infusions of the μ-opioid agonist, DAMGO, markedly increased intake of standard rat chow. When given a choice between palatable fat- versus carbohydrate enriched test diets, intra-vmPFC DAMGO infusions selectively increased carbohydrate intake, even in rats with a baseline fat preference. Rats also exhibited motor hyperactivity characterized by rapid switching between brief bouts of investigatory and ingestive behaviors. Intra-vmPFC DAMGO affected neither water intake nor non-specific oral behavior. Similar DAMGO infusions into neighboring areas of lateral orbital or anterior motor cortex had minimal effects on feeding. Neither stimulation of vmPFC-localized delta-opioid, kappa-opioid, dopaminergic, serotonergic, or noradrenergic receptors, nor antagonism of D1, 5HT1A, or alpha- or beta-adrenoceptors, reproduced the profile of DAMGO effects. Muscimol-mediated inactivation of the vmPFC, and intra-vmPFC stimulation of κ-opioid receptors or blockade of 5HT2A receptors, suppressed motor activity and increased feeding bout duration-a profile opposite to that seen with DAMGO. Hence, μ-opioid-induced hyperphagia and carbohydrate intake can be elicited with remarkable pharmacological and behavioral specificity from discrete subterritories of the frontal cortex. These findings may have implications for understanding affect-driven feeding and loss of restraint in eating disorders.