The dopamine D1 receptor is a critical mediator for cocaine-induced gene expression.
The dopamine D1 receptor plays a major role in mediating behavioral responses to cocaine administration. The time course for the acquisition and the relative stability for the expression of behavioral responses suggest the involvement of enduring neuroadaptations in response to repeated cocaine exposure. Changes in gene expression through the D1 receptors may accompany and mediate the development of such neuroadaptations to repeated cocaine stimulation. To test this possibility, we systematically compared the expression of the fos and Jun family immediate early genes in the nucleus accumbens and caudoputamen in D1 receptor mutant and wild-type control mice after acute and repeated cocaine exposure. Moreover, we compared the expression of three molecules that have been implicated in mediating the actions of cocaine, Galphaolf, beta-catenin and brain-derived neurotrophic factor, in the two groups of mice before and after cocaine administration. We found that there is a lack of induction of c-Fos, FosB, Fra-2 and JunB by acute cocaine exposure, and of DeltaFosB by repeated cocaine administration in both the NAc and CPu of D1 receptor mutant mice compared with wild-type control mice. Moreover, the D1 receptor is differentially required for mediating Galphaolf, beta-catenin and BDNF expression in the NAc and CPu upon cocaine exposure. These results suggest that the D1 receptor is a critical mediator for cocaine-induced expression of these genes.
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D044385:GTP-Binding Protein alpha Subunits; D015870:Gene Expression / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D017781:Genes, Immediate-Early / Q000187:drug effects; D020962:Heterotrimeric GTP-Binding Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000096:biosynthesis; D051176:beta Catenin
D019208:Brain-Derived Neurotrophic Factor; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D044385:GTP-Binding Protein alpha Subunits; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D017447:Receptors, Dopamine D1; D015534:Trans-Activators; D051176:beta Catenin; C084618:olfactory G protein subunit alpha olf; D020962:Heterotrimeric GTP-Binding Proteins; D003042:Cocaine