Järbe T U C, DiPatrizio N V
Temple University, Department of Psychology, Philadelphia, Pennsylvania, USA.
Behav Pharmacol. 2005 Sep;16(5-6):373-80. doi: 10.1097/00008877-200509000-00009.
This study examined effects of the CB1 receptor antagonist/inverse agonist SR-141716 and the CB1 receptor agonist delta9-tetrahydrocannabinol (delta9-THC) on feeding behavior in male Sprague-Dawley rats. Rats were housed individually with free access to regular pelletized laboratory chow [after a 2 weeks handling phase, animals had access to regular chow for 21 h (Study 1) or 22 h (Study 2); high-fat powder food for 3 h in Study 1 and 2 h in Study 2, respectively], and free access to water. Animals were maintained on a reversed 12-h light/dark cycle (dark beginning at noon). Rats were habituated to this type of feeding and light/dark schedule for 3 weeks until a stable baseline for food intake was achieved. In Study 1, animals were examined after administration of delta9-THC alone (dose range 0.1-1.8 mg/kg), SR-141716 alone (dose range 0.03-0.3 mg/kg), and the two drugs combined; injections were given i.p. at the beginning of the second hour after presenting the high-fat diet and drugs were given twice weekly. There was a dose-related increase in high-fat diet intake, peaking at 0.56-1 mg/kg delta9-THC. SR-141716 alone suppressed the high-fat diet intake below control levels. A combination of 0.3 mg/kg SR-141716 and 0.56 mg/kg delta9-THC counteracted the effects on consumption of either drug alone. In Study 2, experimental rats were treated initially with 0.56 mg/kg delta9-THC for six consecutive days; controls received vehicle. Attenuation of the hyperphagia (high-fat diet) was evident after the second injection. Increasing doses of delta9-THC (1 and 1.8 mg/kg, for two and three consecutive days, respectively) did not reinstate the initial hyperphagia. In conclusion, low-to-moderate doses of delta9-THC produced hyperphagia (to a high-fat food source), which was antagonized by SR-141716. SR-141716 singly suppressed intake of the high-fat diet. Delta9-THC-induced hyperphagia dissipated rapidly upon chronic treatment; however, it is unclear whether this reflects pharmacological tolerance or the emergence of a conditioned taste aversion in Study 2.
本研究考察了CB1受体拮抗剂/反向激动剂SR - 141716和CB1受体激动剂δ9 - 四氢大麻酚（δ9 - THC）对雄性Sprague - Dawley大鼠进食行为的影响。大鼠单独饲养，可自由摄取常规颗粒状实验室饲料[经过2周的适应期后，动物在研究1中有21小时（研究1）或22小时（研究2）可获取常规饲料；在研究1中3小时、研究2中2小时可获取高脂粉末食物]，并可自由饮水。动物维持12小时颠倒的明暗循环（中午开始为暗）。大鼠适应这种进食和明暗时间表3周，直至达到稳定的食物摄入量基线。在研究1中，单独给予δ9 - THC（剂量范围0.1 - 1.8毫克/千克）、单独给予SR - 141716（剂量范围0.03 - 0.3毫克/千克）以及两种药物联合给药后对动物进行检测；在提供高脂饮食后第二小时开始腹腔注射，药物每周给药两次。高脂饮食摄入量呈剂量相关增加，在0.56 - 1毫克/千克δ9 - THC时达到峰值。单独使用SR - 141716可将高脂饮食摄入量抑制至对照水平以下。0.3毫克/千克SR - 141716与0.56毫克/千克δ9 - THC联合使用可抵消两种药物单独使用时对摄入量的影响。在研究2中，实验大鼠最初连续6天接受0.56毫克/千克δ9 - THC治疗；对照组给予溶剂。第二次注射后，多食症（高脂饮食）明显减轻。增加剂量的δ9 - THC（分别为1和1.8毫克/千克，连续给药2天和3天）并未恢复最初的多食症。总之，低至中等剂量的δ9 - THC会导致多食症（针对高脂食物来源），这可被SR - 141716拮抗。单独使用SR - 141716可抑制高脂饮食的摄入量。慢性治疗后，δ9 - THC诱导的多食症迅速消失；然而，尚不清楚这是反映了药理学耐受性还是研究2中出现了条件性味觉厌恶。
