Dopamine D1 receptor, but not dopamine D2 receptor, is a critical regulator for acute cocaine-enhanced gene expression.
OBJECTIVE
The aim of present study is to investigate the roles of dopamine receptor subfamilies and their subsequent molecular events in cocaine-enhanced gene expression in striatum.


METHODS
Acute cocaine-treated mice models were build to address this issue. Specific antagonists for dopamine D1 and D2 receptors (SCH 23390 and raclopride, respectively) and specific inhibitor for extracellular signal-regulated protein kinase 1/2 (ERK1/2) kinase were pretreated. Immunofluorescence was used to detect the expressions of c-Fos, phosphorylated cAMP response element binding (p-CREB) and phosphorylated Elk-1 (p-Elk-1) in striatum.


RESULTS
Acute cocaine injection significantly enhanced expressions of c-Fos, p-CREB and p-Elk-1 in the striatum. Notably, these enhancements were totally blocked to normal level by SCH 23390 pre-treatment, while no changes occurred in the presence of raclopride. Moreover, we found that dopamine D1 receptor was involved in acute cocaine-induced activation of ERK1/2 in the striatum. Blockade of this dopamine D1 receptor-dependent ERK1/2 activation by SL 327 could reduce cocaine-enhanced expressions of c-Fos, p-CREB and p-Elk-1 in the striatum.


CONCLUSIONS
These results suggest that dopamine D1 receptor, but not dopamine D2 receptor, plays a critical role in regulating acute cocaine-enhanced gene expression in the striatum, and ERK1/2 pathway may contribute to this regulation.
Guan
Xiaowei
X
Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
Tao
Jin
J
Li
Shengnan
S
D000818:Animals; D050882:CREB-Binding Protein / Q000096:biosynthesis / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050807:ets-Domain Protein Elk-1 / Q000096:biosynthesis / Q000187:drug effects
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050807:ets-Domain Protein Elk-1; D050882:CREB-Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D003042:Cocaine