Crespi F, Corsi M, Reggiani A, Ratti E, Gaviraghi G
Department of Biology, Glaxo Wellcome SpA, Medicines Research Centre, via Fleming 4, 37100 Verona, Italy.
Expert Opin Investig Drugs. 2000 Oct;9(10):2249-58. doi: 10.1517/13543784.9.10.2249.
In the brain, cholecystokinin (CCK) has been described to act as a central neurotransmitter or neuromodulator involved in functions such as food consumption, stress and anxiety. Recently, the CCK system has been involved in drug dependence phenomena and proposed to be correlated to a putative state of 'drug preferring' phenotype within free choice tests. CCK exerts its action in the CNS through at least two different G-protein coupled high affinity receptors, CCK1 and CCK2. Various selective CCK receptor agonists and antagonists have been synthesised. In particular, L-364,718 has been demonstrated to be a potent and selective CCK1 receptor antagonist, whereas L-365,260 is a potent and selective CCK2 receptor antagonist. More recently, GV150013 has been reported to be a highly selective CCK2 receptor antagonist. This paper reviews the putative role of the CCK system within drug dependence phenomena. In particular, it analyses the relationship between central CCK activity and the exhibition of spontaneous preference for drugs of abuse, such as cocaine or alcohol. The potential therapeutic role for CCK receptor antagonists is also discussed.
在大脑中，胆囊收缩素（CCK）被描述为一种参与食物摄入、应激和焦虑等功能的中枢神经递质或神经调节剂。最近，CCK系统已涉及药物依赖现象，并被认为与自由选择试验中假定的“药物偏好”表型状态相关。CCK通过至少两种不同的G蛋白偶联高亲和力受体CCK1和CCK2在中枢神经系统中发挥作用。已经合成了各种选择性CCK受体激动剂和拮抗剂。特别是，L-364,718已被证明是一种强效且选择性的CCK1受体拮抗剂，而L-365,260是一种强效且选择性的CCK2受体拮抗剂。最近，GV150013被报道为一种高度选择性的CCK2受体拮抗剂。本文综述了CCK系统在药物依赖现象中的假定作用。特别是，分析了中枢CCK活性与对可卡因或酒精等滥用药物的自发偏好表现之间的关系。还讨论了CCK受体拮抗剂的潜在治疗作用。
