Mediating effect of dopamine D3 receptors on Jak2 and GABAAalpha1 expression in mouse brains induced by cocaine / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>GABAAalpha1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopamine receptors play an important role in the expression of these genes.</p>

Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the role of dopamine receptors in the regulation of the activity of transcription factor cAMP response element-binding protein (CREB) after cocaine treatment.</p><p><b>METHODS</b>By using dopamine receptor antagonists SCH23390 and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after cocaine treatment and role of extracellular signal-regulated kinase (ERK) in cocaine-induced CREB activation were examined by Western blotting, which was also employed for determination of the effect of SCH23390 and nafadotride on CREB activation.</p><p><b>RESULTS</b>D1 receptor antagonist could inhibit cocaine-induced CREB activation, while D3 receptor antagonist enhanced cocaine-induced CREB activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB activation.</p><p><b>CONCLUSION</b>D1 and D3 dopamine receptors can oppositely regulate CREB activation after cocaine treatment and this regulation depends on ERK signaling pathway.</p>