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Mutating serine\u2010968 to phenylalanine (S968F) in CYFIP2 causes an altered cocaine response in mice. The neuronal mechanisms underlying this response remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>We performed cocaine reward\u2010related behavioural tests and examined changes in synaptic protein phenotypes and neuronal morphology in the nucleus accumbens (NAc), using CYFIP2 S968F knock\u2010in mice to investigate the role of CYFIP2 in regulating cocaine reward.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>CYFIP2 S968F mutation attenuated cocaine\u2010induced behavioural sensitization and conditioned place preference. Cocaine\u2010induced c\u2010Fos was not observed in the NAc of CYFIP2 S968F knock\u2010in mice. However, c\u2010Fos induction was still evident in the medial prefrontal cortex (mPFC). CYFIP2 S968F mutation altered cocaine\u2010associated CYFIP2 signalling, glutamatergic protein expression and synaptic density in the NAc following cocaine exposure. To further determine the role of CYFIP2 in NAc neuronal activity and the mPFC projecting to the NAc activity\u2010mediating reward response, we used optogenetic tools to stimulate the NAc or mPFC\u2010NAc pathway and observed that optogenetic activation of the NAc or mPFC\u2010NAc pathway induced reward\u2010related behaviours. This effect was not observed in the S968F mutation in CYFIP2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These results suggest that CYFIP2 plays a role in controlling cocaine\u2010mediated neuronal function and structural plasticity in the NAc, and that CYFIP2 could serve as a target for regulating cocaine reward.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16427","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T02:18:26Z","timestamp":1715825906000},"page":"3327-3345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The mutated cytoplasmic fragile X messenger ribonucleoprotein 1 (FMR1)\u2010interacting protein 2 (CYFIP2\u2009S968F) regulates cocaine\u2010induced reward behaviour and plasticity in the nucleus 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