Dopamine uptake inhibitors block long-term neurotoxic effects of methamphetamine upon dopaminergic neurons

Brain Res. 1990 Apr 16;513(2):274-9. doi: 10.1016/0006-8993(90)90467-p.

Abstract

A single large dose (100 mg/kg, s.c.) of methamphetamine (MA) is known to exert neurotoxic effects on dopaminergic neurons. The potency at which a series of dopamine (DA) uptake inhibitors blocked MA-induced neostriatal depletions (amfonelic acid (AFA) much greater than mazindol (MAZ) greater than or equal to bupropion (BUP) greater than benztropine (BENZ)) was similar to their potency at blocking 6-hydroxydopamine (6-OHDA) neurotoxicity in rats. Amfonelic acid was able to block long-term neostriatal DA depletions when given 8 h, but not 16 h, after a single large MA dose. These results suggest that an intact and functional DA uptake site is necessary for the development of MA-induced long-term DA depletions.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiology*
  • Dopamine / physiology*
  • Hydroxydopamines / toxicity
  • Indoles / pharmacology*
  • Male
  • Mazindol / pharmacology*
  • Methamphetamine / toxicity*
  • Nalidixic Acid / analogs & derivatives
  • Naphthyridines / pharmacology*
  • Neurotoxins / pharmacology*
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Oxidopamine
  • Rats
  • Rats, Inbred Strains
  • Serotonin / physiology

Substances

  • Hydroxydopamines
  • Indoles
  • Naphthyridines
  • Neurotoxins
  • Neurotransmitter Uptake Inhibitors
  • Serotonin
  • Nalidixic Acid
  • Methamphetamine
  • Oxidopamine
  • Mazindol
  • amfonelic acid
  • Dopamine