Selective monoamine oxidase subtype inhibition and striatal extracellular dopamine in the guinea-pig

1 Striatal microdialysate levels of dopamine (DA) in conscious guinea-pigs were measured following acute (1 day) and chronic (21 days) treatment with deprenyl (2 and 0.25 mg kg(-1) s.c., respectively) or clorgyline (4 and 1 m g kg(-1) s.c., respectively), as well as by combination treatment using the same doses of the two inhibitors. These treatments caused selective inhibi tion of monoamine oxidase type B (MAO-B) or monoamine oxidase type A (MAO-A ) respectively. 2 Neither acute nor chronic treatments with deprenyl or clorgyline increase d basal or KCl-induced DA levels. Acute and chronic clorgyline treatments w ere accompanied by significant reductions in striatal microdialysate 3,4-di hydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). On the other hand, both acute and chronic deprenyl treatments were accompanied by signif icant increases in microdialysate HVA with no effect on DOPAC levels. 3 Acute or chronic combined treatment with clorgyline and deprenyl increase d tissue but not microdialysate DA levels. The combination treatment given chronically also reduced KCl-induced DA release but enhanced amphetamine-in duced DA release. 4 Microdialysate DA levels increased to a smaller extent in guinea-pig than in rat following local striatal infusion of GBR-12909 (100 mu M). 5 The difference between guinea-pigs and rats in the response to GBR-12909, could be the result of a lower dopaminergic innervation and/or density of DA transporter. This difference may explain why striatal microdialysate DA levels increased following chronic deprenyl treatment in the rat but not in the guinea-pig.