Subchronic methamphetamine treatment enchances ouabain-induced striatal dopamine efflux in vivo

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The effect of manipulation of the Na + gradient between the intracellular and extracellular media on striatal dopamine (DA) efflux under steady-state conditions after subchronic methamphetamine (MAP) treatment was investigated. Rats were injected with 4 mg/kg MAP or saline (i.p.), once daily for 14 days. Seven days after the last injection, ouabain (10 −4 M), a selective inhibitor of the Na +,K +-ATPase, was infused locally through a semi-permeable probe in the striatum. Ouabain induced a significantly greater ( P < 0.01) increase of the DA concentrations in the striatal perfusate in the subchronic MAP than the control group. The levels of 3,4-dihydroxyphenylacetic acid (DOPAC) ( P < 0.05) and 5-hydroxyindoleacetic acid (5-HIAA) ( P < 0.05) were significantly higher in the subchronic MAP than in the control group. Reserpine pretreatment (5 mg/kg, i.p.) did not affect the enhanced ouabain-induced DA efflux ( P < 0.01) in the subchronic MAP group, and the levels of DOPAC ( P < 0.01), 5-HIAA ( P < 0.01) and HVA ( P < 0.01) were also significantly higher in the subchronic MAP than in the control group. In contrast, α-methyl- p-tyrosine (250 mg/kg, i.p.) pretreatment abolished the ouabain-induced efflux of DA, DOPAC and HVA, but not 5-HIAA, in both groups. Specific striatal [ 3H]ouabain binding and striatal Na +,K +-ATPase activity in the subchronic MAP and control groups did not differ significantly. These results suggest that subchronic MAP treatment facilitates the efflux of newly synthesized DA, which is induced by the ouabain-induced decrease of the Na + gradient between intracellular and extracellular media. The Na + gradient may, therefore, play an important role in the efflux of DA after subchronic MAP treatment.