Release of endogenous dopamine from rat isolated striatum: effect of clorgyline and (-)-deprenyl

Abstract

High performance liquid chromatography with electrochemical detection was used to measure the release and content of dopamine and dihydroxyphenylacetic acid (DOPAC) from rat isolated striatum. The effects of the monoamine oxidase (MAO) inhibitors clorgyline and (-)-deprenyl on dopamine and DOPAC release and contents, and the IC50 values of these compounds for inhibition of dopamine deamination in rat striatum were determined. Dopamine release was significantly increased by elevated KCl (22 mM) in a Ca2+-dependent manner, and by ouabain (20 muM), whereas the release of DOPAC remained constant. The loss in striatal dopamine content during the incubation period (67% of initial content) was far greater than the amount of dopamine recovered in the incubation fluid (16% of initial content), suggesting that much of the DOPAC, released during incubation originated from the conversion of dopamine to DOPAC within the striatum. A concentration-dependent decrease in DOPAC efflux, both during rest and stimulation periods, was observed in the presence of clorgyline (10(-8)M-10(-7)M) and (-)-deprenyl (10(-5)M-10(-4)M). Higher concentrations of clorgyline (10(-7)M) and (-)-deprenyl (10(-4)M), which inhibited dopamine deamination by 85-90%, enhanced both the resting and KCl-induced release of dopamine. The total amount of dopamine plus DOPAC that was released in the presence of clorgyline or (-)-deprenyl did not differ from control values, suggesting that the increase in dopamine release elicited by MAO inhibitors might result from reduced degradation of dopamine to DOPAC. 6 The IC50 values of clorgyline (5 x 10-9M) and (-)-deprenyl (5 x 10-6M) for inhibition of dopamine deamination indicate that dopamine is a substrate for type A MAO in rat striatum.