Protection of malonate-induced GABA but not dopamine loss by GABA transporter blockade in rat striatum

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Updated: Sep 30, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
07:16

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission

Published on: August 16, 2018

Gail D Zeevalk1, Lawrence Manzino, Patricia K Sonsalla

  • 1Department of Neurology, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.

Experimental Neurology
|July 3, 2002
PubMed

Insights

GABA transporter blockade protects GABAergic neurons from malonate-induced damage in rats, suggesting potential therapeutic benefits for neurodegenerative diseases like Huntington's disease.

Area of Science:

  • Neuroscience
  • Neuroprotection
  • Mitochondrial function

Background:

  • Overstimulation of GABA(A) receptors can worsen neuronal damage during metabolic stress.
  • GABA(A) antagonists and GABA transport blockers show neuroprotection in vitro.
  • Malonate models neurodegenerative diseases by inhibiting mitochondrial complex II.

Purpose of the Study:

  • To investigate if GABA transporter blockade protects neurons in vivo during mitochondrial impairment.
  • To compare in vivo findings with existing in vitro studies on GABAergic neuroprotection.

Main Methods:

  • Rats received stereotaxic infusion of malonate into the striatum to induce metabolic stress.
  • GABA transport blocker NO711 was administered before and after malonate.
  • Striatal dopamine and GABA levels were measured after one week.

Main Results:

  • Malonate caused significant loss of striatal dopamine and GABA.
  • GABA transporter blockade attenuated GABA loss but not dopamine loss.
  • GABA(A) or GABA(B) receptor modulation did not affect malonate-induced neuronal loss.

Conclusions:

  • GABA transporter blockade protects GABAergic neurons during mitochondrial impairment in the striatum.
  • This neuroprotection mechanism differs from in vitro findings regarding GABA(A) receptor involvement.
  • GABA transporter blockade may be beneficial for conditions involving energy inhibition, such as stroke or Huntington's disease.

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