Brain microdialysis in rats: a technique to reveal competition in vivo between endogenous dopamine and moclobemide, a RIMA antidepressant.

Abstract

In this study, the effect of the interaction between the short-acting reserpine-like dopamine (DA) releaser Ro 4-1284 (1 mg/kg IP) and the reversible inhibitors of monoamine oxidase type A (MAO-A), moclobemide (Aurorix) and Ro 41-1049 (20 mg/kg IP, each), on the outflow of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) was investigated by rat transstriatal microdialysis. The injection of Ro 4-1284 after MAO-A inhibitors produced a marked increase of DA concentrations corresponding to a bell-shaped change in DOPAC outflow. This effect was more pronounced in rats treated with moclobemide than with Ro 41-1049. These data support the view that the increment of the endogenous substrate DA might displace moclobemide more rapidly than Ro 41-1049 from MAO-A active sites. The microdialysis method is proposed as a more reliable in vivo technique to investigate the degree of reversibility of the reversible MAO-A inhibitors.