Foltin Richard W, Haney Margaret
Division on Substance Abuse, New York State Psychiatric Institute, Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
Pharmacol Biochem Behav. 2007 Apr;86(4):766-73. doi: 10.1016/j.pbb.2007.03.004. Epub 2007 Mar 15.
The purpose of this study was to determine if a cannabinoid CB(1) receptor antagonist would selectively decrease consumption of highly palatable food in non-human primates. The CB(1) receptor antagonist SR141716 (rimonabant; 0.12-1.0 mg/kg, i.m.) and the stimulant anorectic drug d-amphetamine (0.12-1.0 mg/kg, i.m.) were administered to non-food deprived baboons for the purpose of measuring the effect of each drug on consumption of the normal diet, and a large single meal of a high-carbohydrate candy. Four male and four female baboons had access to food 24 h each day, but they had to complete a two phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Three days a week baboons received a jelly sugar-coated candy (Skittles) during the first meal and then pellets were available in subsequent meals. All baboons ate as many individual candies in one meal as they did pellets throughout the entire day. Acute d-amphetamine and, to a lesser extent, SR141716 decreased both candy intake in a single meal and pellet intake in a single meal and over 24 h. d-Amphetamine, but not SR141716, increased latency to the candy meal and the first pellet meal indicating that the two drugs differentially altered feeding topography. Although males ate more food pellets than females, few other sex differences were observed. Thus, although effective in decreasing food intake, there was no evidence of a specific effect of CB(1) receptor antagonism on consumption of a large meal or a palatable food.
本研究的目的是确定大麻素CB(1)受体拮抗剂是否会选择性降低非人灵长类动物对高适口性食物的摄入量。将CB(1)受体拮抗剂SR141716（利莫那班；0.12 - 1.0毫克/千克，肌肉注射）和刺激性食欲抑制药物d - 苯丙胺（0.12 - 1.0毫克/千克，肌肉注射）给予未处于食物剥夺状态的狒狒，以测量每种药物对正常饮食以及一顿高碳水化合物糖果大餐摄入量的影响。四只雄性和四只雌性狒狒每天有24小时的进食时间，但它们必须完成一个两阶段的操作性程序才能进食。在30分钟的食欲阶段，动物需要在一个杠杆上做出反应，之后才能开始进食阶段，在进食阶段，在另一个杠杆上做出反应会导致食物供应，即一顿饭。每周三天，狒狒在第一餐时会得到裹有糖衣的果冻糖果（彩虹糖），随后的餐食提供颗粒饲料。所有狒狒在一顿饭中吃的单个糖果数量与它们一整天吃的颗粒饲料数量相同。急性给予d - 苯丙胺以及在较小程度上给予SR141716，均可降低一顿饭中的糖果摄入量以及一顿饭和24小时内的颗粒饲料摄入量。d - 苯丙胺而非SR141716增加了进食糖果餐和第一顿颗粒饲料餐的延迟时间，这表明这两种药物对进食行为的影响存在差异。虽然雄性比雌性吃更多的颗粒饲料，但未观察到其他明显的性别差异。因此，尽管CB(1)受体拮抗剂在减少食物摄入量方面有效，但没有证据表明其对大餐或适口性食物的摄入有特异性影响。
