Involvement of cholecystokinin within craving for cocaine: role of cholecystokinin receptor ligands

In the brain, cholecystokinin (CCK) has been described to act as a central neurotransmitter or neuromodulator involved in functions such as food consu mption, stress and anxiety. Recently, the CCK system has been involved in d rug dependence phenomena and proposed to be correlated to a putative state of 'drug preferring' phenotype within free choice tests. CCK exerts its act ion in the CNS through at least two different G-protein coupled high affini ty receptors, CCK1 and CCK2. Various selective CCK receptor agonists and an tagonists have been synthesised. In particular, L-364,718 has been demonstr ated to be a potent and selective CCK1 receptor antagonist, whereas L-365,2 60 is a potent and selective CCK2 receptor antagonist. More recently, GV150 013 has been reported to be a highly selective CCK2 receptor antagonist. Th is 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.