Dela Cruz J A D, Coke T, Icaza-Cukali D, Khalifa N, Bodnar R J
Behavioral and Cognitive Neuroscience Cluster, Psychology Doctoral Program, The Graduate Center, City University of New York, United States.
Department of Psychology, Queens College, City University of New York, United States.
Neurobiol Learn Mem. 2014 Oct;114:223-30. doi: 10.1016/j.nlm.2014.07.004. Epub 2014 Jul 25.
Animals learn to prefer flavors associated with the intake of sugar (sucrose, fructose, glucose) and fat (corn oil: CO) solutions. Conditioned flavor preferences (CFP) have been elicited for sugars based on orosensory (flavor-flavor: e.g., fructose-CFP) and post-ingestive (flavor-nutrient: e.g., intragastric (IG) glucose-CFP) processes. Dopamine (DA) D1, DA D2 and NMDA receptor antagonism differentially eliminate the acquisition and expression of fructose-CFP and IG glucose-CFP. However, pharmacological analysis of fat (CO)-CFP, mediated by both flavor-flavor and flavor-nutrient processes, indicated that acquisition and expression of fat-CFP were minimally affected by systemic DA D1 and D2 antagonists, and were reduced by NMDA antagonism. Therefore, the present study examined whether systemic DA D1 (SCH23390), DA D2 (raclopride) or NMDA (MK-801) receptor antagonists altered acquisition and/or expression of CFP induced by oral glucose that should be mediated by both flavor-flavor and flavor-nutrient processes. Oral glucose-CFP was elicited following by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in 8% glucose and another flavor (CS-, e.g., grape) mixed in 2% glucose. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 days. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 2% glucose occurred 0.5 h after systemic administration of vehicle (VEH), SCH23390 (50-800 nmol/kg), raclopride (50-800 nmol/kg) or MK-801 (50-200 μg/kg). Rats displayed a robust CS+ preference following VEH treatment (94-95%) which was significantly though marginally attenuated by SCH23390 (67-70%), raclopride (77%) or MK-801 (70%) at doses that also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH, SCH23390 (50-400 nmol/kg), raclopride (50-400 nmol/kg) or MK-801 (100 μg/kg) 0.5 h prior to ten 1-bottle training trials with CS+/8%G and CS-/2%G training solutions that was followed by six 2-bottle CS+ vs. CS- tests in 2% glucose conducted without injections. The significant and persistent CS+ preferences observed in the VEH (94-98%) group was significantly reduced by rats receiving SCH23390 at 400 nmol/kg (65-73%), raclopride at 200 or 400 nmol/kg (76-82%) or MK-801 at 100 μg/kg (68-69%). Thus, systemic DA D1 and DA D2 receptor antagonism produced smaller reductions in the expression of oral glucose-CFP relative to fructose-CFP or IG-glucose-CFP. Correspondingly, systemic DA D1, DA D2 and NMDA receptor antagonism also produced smaller reductions in the acquisition of oral glucose-CFP relative to fructose-CFP or IG-glucose-CFP. These data suggest, but do not prove, that the magnitude and persistence of these receptor antagonist effects upon sugar-CFP might depend upon the individual or combined engagement of flavor-flavor and flavor-nutrient processes.
动物会学会偏好与摄入糖(蔗糖、果糖、葡萄糖)溶液和脂肪(玉米油:CO)溶液相关的味道。基于口部感官(味道 - 味道:例如,果糖 - 条件性味道偏好)和摄食后(味道 - 营养物质:例如,胃内(IG)葡萄糖 - 条件性味道偏好)过程,已引发了对糖的条件性味道偏好(CFP)。多巴胺(DA)D1、DA D2和N - 甲基 - D - 天冬氨酸(NMDA)受体拮抗剂对果糖 - CFP和IG葡萄糖 - CFP的习得和表达有不同程度的消除作用。然而,对由味道 - 味道和味道 - 营养物质过程介导的脂肪(CO) - CFP进行的药理学分析表明,全身给予DA D1和D2拮抗剂对脂肪 - CFP的习得和表达影响极小,而NMDA拮抗剂可使其降低。因此,本研究考察了全身给予DA D1(SCH23390)、DA D2(雷氯必利)或NMDA(MK - 801)受体拮抗剂是否会改变由口服葡萄糖诱导的CFP的习得和/或表达,口服葡萄糖诱导的CFP应由味道 - 味道和味道 - 营养物质过程介导。通过训练大鼠饮用一种混合于8%葡萄糖中的新味道(条件刺激 +,例如樱桃味)和另一种混合于2%葡萄糖中的味道(条件刺激 -,例如葡萄味)来引发口服葡萄糖 - CFP。在表达研究中,限食的大鼠在10天内每天进行一次一瓶试验(2小时)饮用这些溶液。在全身给予溶剂(VEH)、SCH23390(50 - 800 nmol/kg)、雷氯必利(50 - 800 nmol/kg)或MK - 801(50 - 200 μg/kg)0.5小时后,随后进行两瓶试验,将条件刺激 + 和条件刺激 - 味道混合于2%葡萄糖中。VEH处理后大鼠表现出强烈的条件刺激 + 偏好(94 - 95%),而在能显著降低总体条件刺激摄入量的剂量下,SCH23390(67 - 70%)、雷氯必利(77%)或MK - 801(70%)使这种偏好虽有显著但只是轻微减弱。在单独的习得研究中,大鼠在进行十次一瓶训练试验(使用条件刺激 +/8%葡萄糖和条件刺激 -/2%葡萄糖训练溶液)前0.5小时接受VEH、SCH23390(50 - 400 nmol/kg)、雷氯必利(50 - 400 nmol/kg)或MK - 801(100 μg/kg),随后在不注射的情况下进行六次两瓶条件刺激 + 与条件刺激 - 的2%葡萄糖试验。在VEH组(94 - 98%)中观察到的显著且持续的条件刺激 + 偏好,在接受400 nmol/kg SCH23390的大鼠中显著降低(65 - 73%),在接受200或400 nmol/kg雷氯必利的大鼠中降低(76 - 82%),在接受100 μg/kg MK - 801的大鼠中降低(68 - 69%)。因此,相对于果糖 - CFP或IG - 葡萄糖 - CFP,全身给予DA D1和DA D2受体拮抗剂对口服葡萄糖 - CFP表达的降低幅度较小。相应地,相对于果糖 - CFP或IG - 葡萄糖 - CFP,全身给予DA D1、DA D2和NMDA受体拮抗剂对口服葡萄糖 - CFP习得的降低幅度也较小。这些数据表明,但并未证明,这些受体拮抗剂对糖 - CFP的作用程度和持续性可能取决于味道 - 味道和味道 - 营养物质过程的单独或共同参与。