BACKGROUNDCocaine 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.

METHODSFor 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.

RESULTSTwenty-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.

CONCLUSIONSGABAAalpha1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.

Animals ; Brain ; drug effects ; metabolism ; Cocaine ; pharmacology ; Female ; Gene Expression Regulation ; drug effects ; Immunohistochemistry ; Janus Kinase 2 ; analysis ; genetics ; Male ; Mice ; Receptors, Dopamine D3 ; physiology ; Receptors, GABA-A ; analysis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To study the role of dopamine D3 receptor involved in the amphetamine-induced conditioned place preference (CPP) in mice. METHODS: The CPP was observed in D3 receptor knock-out (D3RKO) mice and C57BL/6 wild-type control mice after administration of amphetamine. The data were analyzed with a two-way ANOVA using the SPSS 13.0 software. RESULTS: D3RKO mice showed a significant amphetamine-induced CPP (P<0.001), compared with the ones administered with saline in C57BL/6 control mice. CONCLUSION The results indicate that amphetamine can produce significant CPP in dopamine D3 receptor knock-out mice, suggesting that amphetamine-induced addiction can be inhibited by dopamine D3 receptor.
Amphetamine/pharmacology* ; Animals ; Behavior, Animal/drug effects* ; Conditioning, Operant/drug effects* ; Disease Models, Animal ; Female ; Gene Knockout Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects* ; Reaction Time ; Receptors, Dopamine D3/physiology*