Comparison of the effects of intracerebrally administered MPP + (1-methyl-4-phenylpyridinium) in three species: microdialysis of dopamine and metabolites in mouse, rat and monkey striatum

Abstract

Intracerebral microdialysis in 3 awake species allowed the measurement of the basal output of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole-acetic acid (5-HIAA) from rat and mouse striatum and monkey caudate in vivo. The DOPAC/HVA ratios in dialysates from mouse and rat striatum were about 1 and 2 respectively, but only 0.09 in monkey caudate dialysates. The extracellular levels of the metabolites correlated well with reported tissue levels, while extracellular DA levels were 3 orders of magnitude lower than tissue concentrations. The effects of the intracerebrally administered dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP +) were essentially similar in the 3 species. In all cases an immediate, massive release of DA was accompanied by a pronounced decrease in the output of the metabolites. Basal DA release was no longer detectable 5–12 h after MPP + administration and a second MPP + perfusion failed to increase the release of DA.