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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 expressionchange is poorly understood.To identify the changes in gene expression induced by repeated cocaine exposure throughD3 dopamine receptors,we compared the expression of four molecules:Janus kinase 2 (Jak2),g-aminobutanoic acidreceptor subunit alpha 1 (GABAAα1),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) andcaudoputamen (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,nafadotride0.5 mg/kg+cocaine 30 mg/kg,nafadotride 0.5 mg/kg,and saline as the basal group.The expression of Jak2,GABAAα1,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 GABAAα1decreased in cocaine group compared with basal line and further decreased in the cocaine+nafadotride group andremained at basal level in the nafadotride group.Similarly,the Jak2 expression decreased in cocaine group comparedwith base line.However,the levels of Jak2 increased in cocaine+nafadotride group compared with cocaine group,whileremained at basal level in nafadotride group.Conclusions GABAAα1 and Jak2 may be involved in chronic cocaine induced neuroadaptations.D3 dopaminereceptors play an important role in the expression of these genes.
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 (GABAAα1), 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 caudututamen (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, GABAAα1, GluR 3 and SDF1 were assayed by Weste rn blot, quantitative real-time RT-PCR and immunohistochemistry. Results Twenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAA alpha 1 decreased in cocaine group compared with basal line and further decreased in the cocaine + nafadotride group and revised 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 remised at basal level in nafadotride group. Confc GABAAα1 and Jak2 may be involved in chronic cocaine-induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.