Summary.
Formation of 6-hydroxydopamine (6-OHDA) has been posited in the striatum following methamphetamine treatment and plays a critical role in methamphetamine-induced nigrostriatal dopaminergic toxicity. We used high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to determine the formation of 6-OHDA by the treatments of methamphetamine combined with pargyline, a monoamine oxidase inhibitor, and pyrogallol, a catechol-O-methyl-transferase inhibitor, in female C57BL/6J mouse striatum. A substantial amount of 6-OHDA (9.9 ± 0.7 pg/mg wet tissue) was detected in mice treated with pargyline (100 mg/kg) and pyrogallol (25 mg/kg) in combination. Greater striatal 6-OHDA levels were observed in mice treated with combined pargyline, pyrogallol and methamphetamine (50 mg/kg) as compared to mice treated with combined pargyline and pyrogallol. However, mice treated with pargyline and pyragollol in combination followed by one and two doses of methamphetamine exhibited comparable striatal 6-OHDA levels (23.2 ± 4.3, 27.3 ± 1.3 pg/mg wet tissue) in our protocol. We conclude that blockade of the primary metabolic pathways of dopamine by inhibiting both monoamine oxidase and catechol-O-methyl-transferase activities is sufficient to induce 6-OHDA formation in the striatum. Acute 6-OHDA accumulation in the striatum can be potentiated by methamphetamine, a potent dopamine releaser, administration following such metabolic inhibitions.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received May 3, 2002; accepted November 10, 2002
Acknowledgements This study was supported by the NSC of Taiwan (grant No. NSC90-2413-H006-012) to Dr. L. Yu.
Authors' address: Dr. L. Yu, National Cheng Kung University College of Medicine, Institute of Behavioral Medicine, 1 University Rd, Tainan 70101, Taiwan, e-mail: lungyu@mail.ncku.edu.tw
Rights and permissions
About this article
Cite this article
Liao, PC., Kuo, YM., Chang, YC. et al. Striatal formation of 6-hydroxydopamine in mice treated with pargyline, pyrogallol and methamphetamine. J Neural Transm 110, 487–494 (2003). https://doi.org/10.1007/s00702-002-0829-x
Issue Date:
DOI: https://doi.org/10.1007/s00702-002-0829-x