In the brain, cholecystokinin (CCK) has been described as a central neuromodulator peptide involved in such functions as anxiety, stress, food consumption, learning, memory storage and opiate analgesia modulation. From existing evidence, we also know that the CCK system is involved with drug dependence phenomena, and that it is correlated with a putative ‘drug-preferring’ phenotype within free choice tests. CCK exerts its action on the central nervous system through at least two different, G-protein-coupled, high-affinity receptors: CCK-A and CCK-B. The mouse CCK-B receptor gene has been cloned, and targeted disruption of this gene has been achieved (via CCK-B knockout mice). Animals without CCK-B receptors display learning disabilities, disturbances in the development of gastric mucosa, and changes to the function of the brain’s dopaminergic system.

In this study, we found differences in the effects of amphetamine, morphine and naloxone on the behavior of CCK-B knockout mice in comparison with wild-type age- and sex-matched littermates, in both conditioned place preference (CPP) and conditioned place average (CPA) tests. The CPP test is based on the association of a putative reward with a set of neutral enviromental cues. When given a choice, wild-type mice spent more time in an environment where they were previously under the influence of a reinforcing drug. Knockout mice did not display such a preference. In the CPA test with naloxone, wild-type animals showed a significant aversion to the drug-paired compartment of the test apparatus, whereas knockout mice did not.

Paper presented at Measuring Behavior 2002 , 4^th International Conference on Methods and Techniques in Behavioral Research, 27-30 August 2002, Amsterdam, The Netherlands

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