biostudies-literatureVorspan FAgence Nationale de la RechercheAgence Nationale de la Recherche (French National Research Agency)381https://www.ebi.ac.uk/biostudies/studies/S-EPMC7648099biostudies-literatureUnknown10(1)Motor disturbances strongly increase the burden of cocaine use disorder (CUDs). The objective of our translational study was to identify the genes and biological pathways underlying the tolerance to cocaine-induced motor effects. In a 5-day protocol measuring motor tolerance to cocaine in rats (N = 40), modeling the motor response to cocaine in patients, whole-genome RNA sequencing was conducted on the ventral and dorsal striatum to prioritize a genetic association study in 225 patients with severe CUD who underwent thorough phenotypic (cocaine-induced hyperlocomotion, CIH; and cocaine-induced stereotypies, CIS) and genotypic [571,000 polymorphisms (SNPs)] characterization. We provide a comprehensive description of the rat striatal transcriptomic response to cocaine in our paradigm. RepeatTranslational psychiatryTranslational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances.PMC7648099ANR-13-NEUR-0001-03ANR-17-NEU3-0002-05Bellivier FIcick RBlugeon CMarie-Claire CBenturquia NFirmo CBloch VMegarbane BVorspan FCourtin CMekdad NPrince NLaplanche JLPishalin DfalseTranslational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances.Motor disturbances strongly increase the burden of cocaine use disorder (CUDs). The objective of our translational study was to identify the genes and biological pathways underlying the tolerance to cocaine-induced motor effects. In a 5-day protocol measuring motor tolerance to cocaine in rats (N = 40), modeling the motor response to cocaine in patients, whole-genome RNA sequencing was conducted on the ventral and dorsal striatum to prioritize a genetic association study in 225 patients with severe CUD who underwent thorough phenotypic (cocaine-induced hyperlocomotion, CIH; and cocaine-induced stereotypies, CIS) and genotypic [571,000 polymorphisms (SNPs)] characterization. We provide a comprehensive description of the rat striatal transcriptomic response to cocaine in our paradigm. Repeat2020-01-01T00:00:00Z2020 Nov2026-05-01T01:35:21.565Z2020-11-19T13:37:26ZS-EPMC76480993315904110.1038/s41398-020-01050-7