Reduced Gi and Go protein function in the rat nucleus accumbens attenuates sensorimotor gating deficits

Kerry E. Culm, Antonio M. Lim, Julie A. Onton, Ronald P. Hammer

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Prepulse inhibition of the acoustic startle response (PPI) is a cross-species measure of sensorimotor gating, which is severely disrupted in patients with schizophrenia. PPI deficits can be produced in experimental animals by administration of selective D2-like dopamine receptor agonists in the nucleus accumbens (NAc). G proteins coupled to these receptors reportedly are altered in the NAc of patients with schizophrenia. Therefore, we sought to determine whether experimental inactivation of intracellular G proteins in the NAc alters PPI. In adult male Sprague-Dawley rats, baseline PPI was determined by presenting acoustic pulse stimuli (120 dB) alone or preceded 100 ms earlier by prepulse stimuli (3, 6 or 12 dB above 70 dB ambient noise). PPI disruption was assessed in the presence of quinpirole (0.0, 0.05, 0.1, 0.5 mg/kg, sc), and pertussis toxin (PTX; 0.05 μg/side) was then infused into the NAc bilaterally. Ten days later, quinpirole-mediated disruption of PPI was significantly reduced; neither PTX alone, nor heat-inactivated PTX had any effect on quinpirole-induced PPI reductions. PPI was significantly higher after PTX infusion upon moderate quinpirole challenge, suggesting that D 2-like receptors were less effective. PTX treatment significantly reduced basal and dopamine-stimulated [35S]GTPγS binding in the NAc core and shell, and reduced G protein immunoreactivity in the NAc. The results suggest that PPI disruption mediated by D2-like receptor activation in the NAc depends on coupling to Gi and Go proteins, alteration of which could cause sensorimotor gating deficits in schizophrenia.

Original languageEnglish (US)
Pages (from-to)12-18
Number of pages7
JournalBrain Research
Volume982
Issue number1
DOIs
StatePublished - Aug 22 2003
Externally publishedYes

Keywords

  • G protein
  • Pertussis toxin
  • Prepulse inhibition
  • Schizophrenia
  • [S]GTPγS

ASJC Scopus subject areas

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

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