Mediating effect of dopamine D3 receptors on Jak2 and GABAAalpha1 expression in mouse brains induced by cocaine.
BACKGROUND
Cocaine addiction may involve complex neuroadaptations, including many changes of genes expression. Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced gene expression change is poorly understood. To identify the changes in gene expression induced by repeated cocaine exposure through D3 dopamine receptors, we compared the expression of four molecules: Janus kinase 2 (Jak2), g-aminobutanoic acid receptor subunit alpha 1 (GABAAalpha1), glutamate receptor AMPA3 alpha 3 (GluR 3) and stromal cell derived factor 1 (SDF1). These four have been implicated in mediating the actions of cocaine in the nucleus accumbens (NAc) and caudoputamen (CPu) in mice after acute and repeated cocaine exposure.


METHODS
For the acute and repeated injections, the mice were divided into four groups: 30 mg/kg cocaine, nafadotride 0.5 mg/kg + cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal group. The expression of Jak2, GABAAalpha1, GluR 3 and SDF1 were assayed by Western blot, quantitative real-time RT-PCR and immunohistochemistry.


RESULTS
Twenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAAalpha1 decreased in cocaine group compared with basal line and further decreased in the cocaine + nafadotride group and remained at basal level in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine group compared with base line. However, the levels of Jak2 increased in cocaine + nafadotride group compared with cocaine group, while remained at basal level in nafadotride group.


CONCLUSIONS
GABAAalpha1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.
Liu
Nu-yun
NY
College of Traditional Chinese Medicine, Department of Pathophysiology, Key Laboratory of Guangdong Proteome Analysis, Southern Medical University, Guangzhou 510515, China.
Zhang
Lu
L
Zhang
Lin
L
Wang
Xiao-ning
XN
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D053614:Janus Kinase 2 / Q000032:analysis / Q000235:genetics*; D008297:Male; D051379:Mice; D050637:Receptors, Dopamine D3 / Q000502:physiology*; D011963:Receptors, GABA-A / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C546241:Gabra1 protein, mouse; D050637:Receptors, Dopamine D3; D011963:Receptors, GABA-A; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D003042:Cocaine