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Molecular and Chemical Neuropathology

, Volume 24, Issue 1, pp 31–41 | Cite as

Effects of pargyline and pyrogallol on the methamphetamine-induced dopamine depletion

  • Taizo Kita
  • George C. Wagner
  • Martin A. Philbert
  • Linda A. King
  • Herbert E. Lowndes
Original Articles

Abstract

The formation of 6-hydroxydopamine (6-OHDA) from dopamine (DA) was investigated in the striatum of male Sprague-Dawley rats following a single administration of methamphetamine hydrochloride (100 mg/kg, sc). Rats were sacrificed 30, 60, and 90 min, and 1 wk after injection, and striatal 6-OHDA, DA, and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by HPLC with electrochemical detection. Methamphetamine decreased striatal DA and DOPAC levels (to 65 and 50% at 90 min, respectively) in the time-course study and also resulted in a long-lasting dopamine depletion (34%) 1 wk after its administration. However, endogenous 6-OHDA formation proved difficult to detect after administration of the methamphetamine alone. Pretreatment with the monoamine oxidase (MAO) inhibitor pargyline (100 mg/kg, ip) and the catechol-O-methyltransferase (COMT) inhibitor pyrogallol (25 mg/kg, ip) resulted in the HPLC detection of a 6-OHDA-like substance 30 min after methamphetamine administration when the oxidizing potential was set at 0.5 V, but not when it was set at 0.2 V. Moreover, pargyline (25 mg/kg, ip) alone or in combination with pyrogallol exacerbated the long-lasting dopamine depletion induced by methamphetamine (50 mg/kg, sc). These results indicate that simultaneous inhibition of MAO and COMT provides a cellular environment that encourages the autoxidation of dopamine to a 6-OHDA-like substance.

Index Entries

Methamphetamine 6-hydroxydopamine dopamine neurotoxicity pargyline pyrogallol monoamine oxidase catechol-O-methyltransferase 

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Copyright information

© Humana Press 1995

Authors and Affiliations

  • Taizo Kita
    • 1
  • George C. Wagner
    • 2
  • Martin A. Philbert
    • 1
  • Linda A. King
    • 2
  • Herbert E. Lowndes
    • 1
  1. 1.Neurotoxicology Laboratories, Department of Pharmacology and ToxicologyThe State UniversityNew Brunswick
  2. 2.Department of Psychology, RutgersThe State UniversityNew Brunswick

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