GABA and dopamine interaction in the basal ganglia: dopaminergic supersensitivity following chronic elevation of brain γ-aminobutyric acid levels

S. P. Sivam, P. M. Hudson, H. A. Tilson, J. S. Hong

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

The influence of chronic activation of the γ-aminobutyric acid (GABA) system on dopaminergic function was evaluated in male rats. Activation of the GABA system was achieved by raising the brain concentration of GABA with aminooxyacetic acid (AOAA), a GABA-transaminase (GABA-T) inhibitor. Repeated i.p. injection (40 or 80 mg/kg/day for 8 days) of AOAA produced a sustained elevation of GABA concentration in the striatum. Beginning 26 h following the last dose of a regimen of AOAA treatment (80 mg/kg/ day for 8 days), the animals exhibited a characteristic spontaneous 'sham-fighting' behavioral stereotypy which peaked at 34 h after the last dose of AOAA; this spontaneous behavior dissipated by 38 h postdose. When challenged with apomorphine, the sham-fighting behavior was interspersed with intense fighting episodes; these precipitated behaviors were evident for up to 2 weeks posttreatment observation period. Animals given a lower dose of AOAA (40 mg/kg/day x 8) did not show signs of spontaneous sham-fighting, but responded with fighting upon apomorphine challenge. Qualitatively similar behavioral effects were obtained when γ-acetylenic GABA (30 mg/kg/day, i.p. for 8 days) was used as the inhibitor of GABA-T. Measurement of dopamine and its acid metabolites in the striatum showed an enhanced turnover of dopamine during the spontaneous behavioral response, suggesting a rebound phenomenon. The levels of 5-hydroxytryptamine or its acid metabolite or neuroactive amino acids such as glutamate, aspartate, taurine, glycine, glutamine in the striatum were not altered by any of the treatments. The behavioral and neurochemical observations indicate that chronic activation of the GABA system leads to the development of dopaminergic supersensitivity, emphasizing the existence of a functional interaction between GABA and dopamine in the basal ganglia. Furthermore, such an interaction may be clinically significant in treatments which require chronic elevation of GABA concentration in the brain.

Original languageEnglish (US)
Pages (from-to)29-35
Number of pages7
JournalBrain research
Volume412
Issue number1
DOIs
StatePublished - May 26 1987
Externally publishedYes

Keywords

  • Apomorphine
  • Basal ganglion
  • Dopamine
  • Sham-fighting behavior
  • Supersensitivity
  • γ-aminobyturic acid (GABA)

ASJC Scopus subject areas

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

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