MPTP-INDUCED BRAIN INDOLEAMINE CHANGES ARE AGE-RELATED AND REGION-DEPENDENT IN RATS

Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in 10 different brain areas was studied in young (1 month old) and aged (21 months old) male rats. Multidose treatment with MPTP (3 mg/kg, i.p. daily for 8 days) caused no changes in 5-HT or 5-HIAA levels in all investigated brain areas of young rats. In contrast, a marked rise in 5-HT concentrations in the dorsal raphe nucleus (DRN), striatum (ST) and nucleus accumbens (NA) as well as a significant depletion of 5-HIAA levels in the preoptic area (POA) was observed in old MPTP-treated rats. MPTP treatment produced a decrease in the 5-HIAA/5-HT ratio in the DRN, ST, NA, POA, substantia nigra (SN) and ventral tegmental area in old rats, while the reduced ratio was found only in the SN and POA of young MPTP-treated rats. In addition, old control rats showed an increased 5-HIAA/5-HT ratio in the DRN as compared to that in young controls. These results indicate that multidose MPTP treatment affects selectively some serotonergic systems of the rat brain, and suggest that the effects of MPTP on serotonergic system in rats may be age-dependent.