Nimodipine and TMB-8 potentiate the AMPA-induced lesion in the basal ganglia

Neurochem Int. 2004 Mar;44(4):287-91. doi: 10.1016/s0197-0186(03)00136-0.

Abstract

Acute injection of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) into the rat globus pallidus leads to calcium precipitation, neuronal death and gliosis. In order to determine whether L-type calcium channels and/or release of Ca(2+) from intracellular stores contribute to the effects of AMPA, nimodipine and 8-(N,N-diethylamino) octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) were administered in combination with AMPA. Nimodipine, but not TMB-8, tended to exacerbate the calcification process initiated by AMPA; the AMPA/nimodipine/TMB-8 combination produced much more calcium deposition than AMPA (+62%, P<0.05). AMPA alone induced a slight but not significant astroglial reaction. Nimodipine slightly enhanced the astroglial reaction triggered by AMPA, whereas TMB-8 doubled it (P<0.001 versus AMPA). These data suggest that blockade of L-type calcium channels by nimodipine enhances calcium imbalance triggered by AMPA, and the calcium release from the endoplasmic reticulum does not participate in the AMPA-induced calcification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / drug effects*
  • Basal Ganglia / pathology
  • Drug Synergism
  • Gallic Acid / analogs & derivatives*
  • Gallic Acid / pharmacology*
  • Male
  • Nimodipine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology*

Substances

  • 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
  • Nimodipine
  • Gallic Acid
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid