Nicotine and its withdrawal alter feeding induced by paraventricular hypothalamic injections of neuropeptide Y in Sprague-Dawley rats

Nicotine and its withdrawal alter feeding induced by paraventricular hypothalamic injections of neuropeptide Y in Sprague-Dawley rats
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DOI:
10.1007/s00213-002-1101-7
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发表时间:
2002-07-01
期刊:
影响因子:
3.4
通讯作者:
Coscina, DV
Coscina, DV
中科院分区:
医学3区
文献类型:
--
作者:
Bishop, C;Parker, GC;Coscina, DV

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原理:吸烟会抑制人类进食和体重,戒烟后往往会反弹。尼古丁(NIC)给药在大鼠中产生类似的作用,但负责的神经机制尚不完全清楚。最近的证据表明,神经肽Y(NPY)的下丘脑水平的变化与NIC管理。下丘脑室旁核(PVN),这通常产生强大的喂养,注射NPY被用来调查PVN-NPY系统的变化,可能有助于NIC的能量平衡的影响。目的:描述NIC治疗与戒断期间PVN-NPY诱导的进食的潜在差异。研究方法:将三组带有单侧PVN插管的雌性大鼠(n=66)植入含有NIC(0、6或12 mg/kg/天)的皮下Alzet微型泵14天。暗发(1800-2000小时)NPY喂养试验进行了5次:植入前、植入后2天和12天以及植入物取出后2天和8天。喂食试验包括在熄灯前1小时的预喂食,然后在PVN注射0.4穆尔盐水或NPY(78 pmol,235 pmol)后进行两次1小时的喂食。结果:NIC最初抑制体重增加,随后稳定恢复,在撤回NIC后短暂夸大。每日喂养急性抑制NIC,但急性增强后NIC停止。PVN-NPY诱导的进食在泵植入后2天被两种剂量的NIC抑制,在泵移除后2天升高,但在泵移除后8天恢复到NIC前的水平。结论:这些发现提供了行为支持,PVN-NPY神经传递的变化可能在NIC的食物摄入和体重调节作用中发挥功能性作用。
Rationale: Cigarette smoking produces feeding and weight suppression in humans that often rebound following cessation. Nicotine (NIC) administration produces similar effects in rats, but the neural mechanisms responsible are not fully known. Recent evidence shows that hypothalamic levels of neuropeptide Y (NPY) change with NIC administration. Infusions of NPY into the paraventricular nucleus of the hypothalamus (PVN), which normally produce robust feeding, were used to investigate changes in the PVN-NPY system that may contribute to NIC's effects on energy balance. Objective: To characterize potential differences in PVN-NPY-induced feeding during NIC treatment versus withdrawal. Methods: Three groups of female rats (n=66) bearing unilateral PVN cannulae were implanted for 14 days with subcutaneous Alzet mini-pumps containing NIC (0, 6, or 12 mg/kg per day). Dark-onset (1800-2000 hours) NPY feeding tests occurred five times: pre-implant, 2 days and 12 days post-implant and 2 days and 8 days after implant removal. Feeding tests consisted of 1 h of pre-feeding prior to lights off, then two 1-h measures of feeding after PVN injections of 0.4 mul saline or NPY (78 pmol, 235 pmol). Results: NIC initially suppressed body weight gain, followed by steady recovery that was briefly exaggerated after withdrawing NIC. Daily feeding was acutely suppressed by NIC but acutely potentiated after NIC cessation. PVN-NPY-induced feeding was suppressed by both doses of NIC 2 days after pump implant, elevated 2 days after pump removal, but returned to pre-NIC levels 8 days after pump removal. Conclusions: These findings provide behavioral support that changes in PVN-NPY neurotransmission may play a functional role in the food intake and weight-modulating effects of NIC.