TY - JOUR T1 - Regulation of the Na<sup>+</sup>/K<sup>+</sup>-ATPase Pump<em>in Vitro</em> after Long-Term Exposure to Cocaine: Role of Serotonin JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 835 LP - 843 VL - 285 IS - 2 AU - Scott A. Mackler AU - Thomas R. Kleyman AU - Xian-Yuan Cha Y1 - 1998/05/01 UR - http://jpet.aspetjournals.org/content/285/2/835.abstract N2 - Long-term exposure to cocaine can cause persistent behavioral changes and alterations in neuronal function. One cocaine-regulated mRNA in the rat brain is the beta-1 subunit of the Na+/K+-ATPase pump. We examined both Na+/K+-ATPase function and expression after cocaine treatment of pheochromocytoma cells. One-hour exposure to cocaine did not alter Na+/K+-ATPase activity, as measured by the ouabain-sensitive component of rubidium uptake. Four days of cocaine resulted in an ∼30% decrease in Na+/K+-ATPase activity. Western blot analyses demonstrated an ∼25% decrease in levels of the beta-1 isoform, without changes in pump total alpha subunit levels. Treatment with dopamine type 1 or type 2 receptor agonists for the same period did not affect Na+/K+-ATPase activity. The serotonin-selective reuptake inhibitor paroxetine caused an ∼45% decrease in rubidium uptake after 4 days, whereas pump function was not altered after treatment with either the dopamine-selective reuptake blocker nomifensine or the norepinephrine-selective reuptake blocker desipramine. Chronic treatment with both cocaine and LY 278,584, a serotonin type 3 receptor antagonist, did not replicate the cocaine-associated decrease in pump function. Long-term cocaine exposure regulates expression and function of the Na+/K+-ATPase pump in neuronal-like cells; this regulation is mediated in part via the serotonin type 3 receptor. Similar Na+/K+-ATPase pump regulation in vivo may selectively alter neuronal function in the mammalian brain. The American Society for Pharmacology and Experimental Therapeutics ER -