Chronic haloperidol administration increases GABA binding and enhances neuronal responsiveness to iontophoresed GABA in rat globus pallidus

Joseph M. Frey, Maharaj K. Ticku, Rodney D. Bell, Ronald D. Huffman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Experiments were conducted to assess the effects of chronic haloperidol (CHAL) administration on γ-aminobutyric acid (GABA) receptor binding within the rat globus pallidus (GP) and on the responsiveness of individual pallidal neurons to microiontophoretically applied GABA and glycine. Rats were administered haloperidol in their food for 30 days in increasing concentrations and the experiments were conducted 2 days after termination of the haloperidol treatment. GABA receptor binding and neuronal responsiveness to GABA were significantly increased within the GP following CHAL treatment. The mean EC50 value for GABA was significantly decreased in the CHAL-treated rats, but there was no change in the EC50 for glycine. Scatchard analysis of [3H]muscimol binding demonstrated a single high-affinity binding site (Kd = 5 nM) within both control and CHAL-treated rats. The binding capacity (Bmax) of this high-affinity site was significantly increased in CHAL-treated rats without any change in the dissociation constant (Kd) for this site. These results suggest that CHAL administration may lead to a decrease in GABA release by striatopallidal efferents. The results of this study, combined with those of our previous study on SNR neurons, have demonstrated that blockade of striatally mediated dopamine (DA) neurotransmission leads to similar changes in GABAergic mechanisms at the level of the GP and SNR and suggest that DA regulation of the striatopallidal and striatonigral GABAergic pathways need not be differentially organized as has previously been postulated.

Original languageEnglish (US)
Pages (from-to)57-67
Number of pages11
JournalBrain Research
Volume491
Issue number1
DOIs
StatePublished - Jul 3 1989

Keywords

  • Chronic haloperidol
  • Globus pallidus
  • Glycine
  • Microiontophoresis
  • Supersensitivity
  • γ-Aminobutyric acid
  • γ-Aminobutyric acid receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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