Effects of ICV administration of the alpha1A-adrenoceptor antagonist 5-methylurapidil on concurrent measures of eating and locomotion after cocaine in the rat.
Effects of ICV administration of the alpha1A-adrenoceptor antagonist 5-methylurapidil on concurrent measures of eating and locomotion after cocaine in the rat.
复制标题
ICV 给予 α1A-肾上腺素受体拮抗剂 5-甲基乌拉地尔对大鼠可卡因后进食和运动的同时测量的影响。
DOI：
10.1016/j.lfs.2007.08.004
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发表时间：
2007
期刊：
影响因子：
6.1
通讯作者：
Wellman,PaulJ
中科院分区：
文献类型：
--
作者：
Clifford,PShane;Davis,KristinaW;Elliott,AudreaE;Wellman,PaulJ
包括安非他明和可卡因在内的精神兴奋剂会诱导运动和刻板行为，并抑制进食。虽然可卡因改变运动的能力通常被认为与多巴胺神经传递有关，但最近的研究表明，通过α 1-肾上腺素能受体（α1-AR）起作用的去甲肾上腺素可以促进可卡因刺激的运动。在迄今发现的三种α1-AR亚型（α1A、α1B和α1D）中，α1B-AR亚型的失活减少了可卡因刺激的运动，而α1A-AR亚型的失活对进食或运动的影响尚不清楚。在本研究中，我们使用并行方法评估了ICV给予α1B-AR拮抗剂5-甲基乌拉地尔（5-MU）对可卡因刺激的过度运动和摄食减少的相对影响[Wellman，P. J.，豪，D.H.戴维斯，K.W.，2005.大鼠摄食和运动的同步测量。行为生理学84（5），769-774。向大鼠ICV输注3种剂量的5-MU（0、3或30 nmol）中的一种，然后注射（i. p.）在5次试验中，每一次试验的可卡因浓度为0、2.5、5.0、10.0或20.0 mg/kg。大鼠总是接受相同的5-MU剂量，但每次试验的可卡因剂量不同。在注射后45分钟内同时评估进食和运动。在2.5 mg/kg可卡因剂量下观察到进食的显著抑制，该剂量不会改变大鼠的向前运动。5-MU给药没有改变用盐水处理的大鼠的运动，但显著增加了基线摄食量。无论是可卡因诱导的食欲减退，也不hypermotorization改变ICV管理的5-MU。这些结果表明，α1-AR激动剂（如苯丙醇胺）抑制进食的能力可能与α1A-AR亚型的激活有关，而可卡因并不通过α1A-AR亚型抑制进食，该亚型也不调节可卡因诱导的过度运动。
Psychostimulants including amphetamine and cocaine induce locomotion and stereotypy and suppress eating. Although the capacity of cocaine to alter locomotion is usually viewed as related to dopamine neurotransmission, recent studies suggest that norepinephrine, acting through alpha1-adrenergic receptors (α1-ARs) can facilitate cocaine-stimulated locomotion. Of the three α1-AR subtypes (α1A, α1B, and α1D) identified to date, inactivation of the α1B-AR subtype diminishes cocaine-stimulated locomotion, whereas the impact of inactivation of the α1A-AR subtype on either eating or locomotion is unknown. In the present study, we assessed the relative impact of ICV administration of the α1B-AR antagonist 5-methylurapidil (5-MU) on cocaine-stimulated hyperlocomotion and hypophagia, using a concurrent method [Wellman, P.J., Ho, D.H., Davis, K.W., 2005. Concurrent measures of feeding and locomotion in rats. Physiology of Behavior 84 (5), 769–774.]. Rats were infused ICV with one of 3 doses of 5-MU (0, 3, or 30 nmol) and then injected (i.p.) with 0, 2.5, 5.0, 10.0, or 20.0 mg/kg cocaine HCl on each of five tests. Rats always received the same 5-MU dose, but a different cocaine dose on each trial. Feeding and locomotion were assessed concurrently during a 45-min postinjection period. Significant suppression of eating was noted at 2.5 mg/kg cocaine, a dose that does not alter forward locomotion in the rat. Administration of 5-MU did not alter locomotion in rats treated with saline, but did significantly increase baseline food intake. Neither cocaine-induced hypophagia nor hyperlocomotion was altered by ICV administration of 5-MU. These results suggest that the capacity of α1-AR agonists (e.g. phenylpropanolamine) to suppress eating may be related to activation of the α1A-AR subtype, whereas cocaine does not act through the α1A-AR subtype to suppress eating nor does this subtype modulate cocaine-induced hyperlocomotion.