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The neural cell adhesion molecule (NCAM) has been related to several neuropsychiatric disorders in humans. Constitutively NCAM\u2010deficient (\u2212\/\u2212) mice display enhanced novelty\u2010induced behavior and hyperfunction of the hypothalamic\u2010pituitary\u2010adrenal axis. Here we hypothesize that NCAM deficiency causes an altered response to cocaine. Cocaine\u2010induced behaviors of NCAM\u2212\/\u2212 mice and wild\u2010type (+\/+) littermates were analyzed in the conditioned place preference (CPP) test. c\u2010fos mRNA levels were investigated by quantitative polymerase chain reaction (qPCR) to measure neural activation after exposure to the cocaine\u2010associated context. NCAM\u2212\/\u2212 mice showed an elevated cocaine\u2010induced sensitization, enhanced CPP, impaired extinction, and potentiated cocaine\u2010induced hyperlocomotion and CPP after extinction. NCAM\u2212\/\u2212 showed no potentiated CPP as compared with NCAM+\/+ littermates when a natural rewarding stimulus (ie, an unfamiliar female) was used, suggesting that the behavioral alterations of NCAM\u2212\/\u2212 mice observed in the CPP test are specific to the effects of cocaine. Activation of the prefrontal cortex and nucleus accumbens induced by the cocaine\u2010associated context was enhanced in NCAM\u2212\/\u2212 compared with NCAM+\/+ mice. Finally, cocaine\u2010induced behavior correlated positively with novelty\u2010induced behavior and plasma corticosterone levels in NCAM\u2212\/\u2212 mice and negatively with NCAM mRNA levels in the hippocampus and nucleus accumbens in wild\u2010type mice. Our findings indicate that NCAM deficiency affects cocaine\u2010induced CPP in mice and support the view that hyperfunction of the stress response system and reactivity to novelty predict the behavioral responses to cocaine.<\/jats:p>","DOI":"10.1111\/adb.12887","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T06:29:05Z","timestamp":1583216945000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hyperfunction of the stress response system and novelty\u2010induced hyperactivity correlate with enhanced cocaine\u2010induced conditioned place preference in NCAM\u2010deficient mice"],"prefix":"10.1111","volume":"26","author":[{"given":"Birgit","family":"K\u00e4hler","sequence":"first","affiliation":[{"name":"Institute for Biosynthesis of Neural Structures, Center for Molecular Neurobiology Hamburg University Medical Center Hamburg\u2010Eppendorf  Hamburg 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