Freedland C S, Sharpe A L, Samson H H, Porrino L J
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Alcohol Clin Exp Res. 2001 Feb;25(2):277-82.
Previous studies have demonstrated that administration of central cannabinoid receptor (CB1) ligands can produce marked effects on ingestive behaviors. However, the possible relationship to ethanol self-administration has not been fully examined. The present series of experiments was designed to characterize further the role of CB1 receptors in appetitive and consummatory behaviors related to sucrose and ethanol.
To determine the relative contribution of CB1 receptors to ethanol seeking and consumption, a series of experiments was designed using the sipper-tube model. In this paradigm, the appetitive and consummatory phases of ethanol and sucrose self-administration are separated. In the appetitive phase, animals are required to complete a response requirement (16 lever presses) within 20 min. If the requirement is successfully completed, access to a sipper tube containing either sucrose or ethanol (consummatory phase) is made available for 20 min.
In the ethanol condition, the CB1 receptor antagonist SR141716A (0.3-3.0 mg/kg, ip) produced dose-related decreases in the probability of response requirement completion without significantly affecting latency to first lever press or overall lever press rate. In the sucrose condition, SR141716A (0.3-3.0 mg/kg, ip) increased first lever press latency without affecting lever press rate. In the consummatory phase, SR141716A (0.3-3.0 mg/kg, ip) administration markedly decreased total intake and the total number of licks for both ethanol and sucrose.
These data indicate that CB1 receptors are involved in mediating both appetitive and consummatory aspects of ingestive behaviors related to sucrose and ethanol.
先前的研究表明,给予中枢大麻素受体(CB1)配体可对摄食行为产生显著影响。然而,其与乙醇自我给药之间的可能关系尚未得到充分研究。本系列实验旨在进一步明确CB1受体在与蔗糖和乙醇相关的食欲和进食行为中的作用。
为确定CB1受体对乙醇寻求和消耗的相对贡献,采用吸管模型设计了一系列实验。在此范式中,乙醇和蔗糖自我给药的食欲和进食阶段是分开的。在食欲阶段,要求动物在20分钟内完成一项反应要求(16次杠杆按压)。如果成功完成该要求,可在20分钟内使用装有蔗糖或乙醇的吸管(进食阶段)。
在乙醇条件下,CB1受体拮抗剂SR141716A(0.3 - 3.0毫克/千克,腹腔注射)使完成反应要求的概率呈剂量依赖性降低,而对首次杠杆按压潜伏期或总体杠杆按压速率无显著影响。在蔗糖条件下,SR141716A(0.3 - 3.0毫克/千克,腹腔注射)增加了首次杠杆按压潜伏期,但不影响杠杆按压速率。在进食阶段,给予SR141716A(0.3 - 3.0毫克/千克,腹腔注射)显著降低了乙醇和蔗糖的总摄入量和总舔舐次数。
这些数据表明,CB1受体参与介导与蔗糖和乙醇相关的摄食行为的食欲和进食方面。