Risco Severiano, Mediavilla Cristina
Departamento de Farmacología, Facultad de Farmacia, Campus de Cartuja, Universidad de Granada, 18071 Granada, Spain.
Departamento de Psicobiologia, Facultad de Psicología, Campus de Cartuja s/n, Universidad de Granada, 18071 Granada, Spain; Cognitive and Behavioural Neuroscience Program, University of Granada, 18071 Granada, Spain.
Pharmacol Biochem Behav. 2014 Nov;126:7-12. doi: 10.1016/j.pbb.2014.09.002. Epub 2014 Sep 16.
Previous studies demonstrated that the intracerebroventricular administration of SB-334867-A, a selective antagonist of orexin OX1R receptors, blocks the acquisition of saccharin-induced conditioned flavor preference (CFP) but not LiCl-induced taste aversion learning (TAL). Orexinergic fibers from the lateral hypothalamus end in the central nucleus of the amygdala (CeA), which expresses orexin OX1R receptors. Taste and sensory inputs also are present in CeA, which may contribute to the development of taste learning. This study analyzed the effect of two doses (1.5 and 6μg/0.5μl) of SB-334867-A administered into the CeA on flavor-taste preference induced by saccharin and on TAL induced by a single administration of LiCl (0.15M, 20ml/kg, i.p.). Outcomes indicate that inactivation of orexinergic receptors in the CeA attenuates flavor-taste preference in a two-bottle test (saccharin vs. water). Intra-amygdalar SB-334867-A does not affect gustatory processing or the preference for the sweet taste of saccharin given that SB-334867-A- and DMSO-treated groups (control animals) increased the intake of the saccharin-associated flavor across training acquisition sessions. Furthermore, SB-334867-A in the CeA does not block TAL acquisition ruling out the possibility that functional inactivation of OX1R receptors interferes with taste processing. Orexin receptors in the CeA appear to intervene in the association of a flavor with orosensory stimuli, e.g., a sweet and pleasant taste, but could be unnecessary when the association is established with visceral stimuli, e.g., lithium chloride. These data suggest that orexinergic projections to the CeA may contribute to the reinforcing signals facilitating the acquisition of taste learning and the change in hedonic evaluation of the taste, which would have important implications for the OX1R-targeted pharmacological treatment of eating disorders.
先前的研究表明，脑室内注射SB - 334867 - A（一种食欲素OX1R受体的选择性拮抗剂）可阻断糖精诱导的条件性味觉偏好（CFP）的形成，但不影响氯化锂诱导的味觉厌恶学习（TAL）。来自下丘脑外侧的食欲素能纤维终止于杏仁核中央核（CeA），该核表达食欲素OX1R受体。味觉和感觉输入也存在于CeA中，这可能有助于味觉学习的发展。本研究分析了向CeA注射两种剂量（1.5和6μg/0.5μl）的SB - 334867 - A对糖精诱导的味觉偏好以及单次注射氯化锂（0.15M，20ml/kg，腹腔注射）诱导的TAL的影响。结果表明，CeA中食欲素能受体的失活会减弱双瓶试验（糖精与水）中的味觉偏好。杏仁核内注射SB - 334867 - A不影响味觉处理或对糖精甜味的偏好，因为SB - 334867 - A处理组和二甲基亚砜处理组（对照动物）在整个训练获取阶段都增加了与糖精相关味道的摄入量。此外，CeA中的SB - 334867 - A并不阻断TAL的形成，排除了OX1R受体功能失活干扰味觉处理的可能性。CeA中的食欲素受体似乎参与了一种味道与口腔感觉刺激（如甜味和愉悦味道）的关联，但当与内脏刺激（如氯化锂）建立关联时可能并非必需。这些数据表明，向CeA的食欲素能投射可能有助于强化信号，促进味觉学习的获取以及味觉享乐评价的改变，这对饮食失调的OX1R靶向药物治疗具有重要意义。
