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EuropeanJournalof Pharmacology, 250 (1993)215-221 Elsevier Science Publishers B.V.

Summary: EuropeanJournalof Pharmacology, 250 (1993)215-221
Elsevier Science Publishers B.V.
EJP 53405
Fluoxetine and desipramine selectively attenuate 2'-NH2-MPTP-induced
depletions in serotonin and norepinephrine
Anne M. Andrews ,,a,b and Dennis L. Murphy a
aLaboratoryof ClinicalScience,National Institute of Mental Health, Bethesda, MD, USA, and 9Departmentof Chemistry,American University,
Washington, DC, USA
Received 5 July1993,accepted 17 September 1993
We recently reported that the novel MPTP analog 1-methyl-4-(2'-aminophenyl)-l,2,3,6-tetrahydropyridine (2'-NHz-MPTP)
administered to C57BL/6 mice produced substantial decreases in forebrain serotonin (5-HT), 5-hydroxyindoleacetic acid
(5-HIAA), and norepinephrine, with negligible effects on brain dopamine or dopamine metabolites. In the present report, we
confirm and extend our original results to include dose-response data and the effect of selective uptake inhibition on the levels of
monoamine neurotransmitters in various regions of the mouse brain following treatment with 2'-NHz-MPTP. In a dose-ranging
study, 2'-NH2-MPTP (10 mg/kg x 4) produced a 25-30% reduction in frontal cortex 5-HT, 5-HIAA, and norepinephrine. When
4 x 20 mg/kg 2'-NHz-MPTP was administered, 70-75% reductions in 5-HT, 5-HIAA, and norepinephrine in both frontal cortex
and hippocampus were seen 1 week after treatment. No changes in dopamine were found in striatum or in any of the other brain
regions examined at either dose. Doses of 40 and 60 mg/kg were lethal shortly after a single injection. In mice receiving either
fluoxetine or desipramine (10 mg/kg) prior to 2'-NHz-MPTP (20 mg/kg× 4), decreases in 5-HT and norepinephrine,
respectively, were significantly attenuated by ~ 30-40%. These data suggest that 2'-NHz-MPTP acts in a dose-dependent


Source: Andrews, Anne M. - Huck Institutes of the Life Sciences, Pennsylvania State University


Collections: Biology and Medicine