title: GABA(B) receptor blockade in the hippocampus affects sensory and sensorimotor gating in Long-Evans rats.
abstract: BACKGROUND
  Sensory and sensorimotor gating deficits are observed in schizophrenia. GABA(B) receptor deficiency is also detected in the hippocampus of schizophrenic patients.
  
  
  OBJECTIVE
  The present study tested the hypothesis that GABA(B) receptors in the hippocampus contribute to paired-pulse gating of hippocampal auditory-evoked potentials (AEP) and auditory prepulse inhibition (PPI) in Long-Evans rats.
  
  
  METHODS
  Gating of hippocampal AEP, or PPI, was examined before and after administration of GABA(B) receptor antagonist, CGP56999A or CGP35348, or saline was administered either systemically (intra-peritoneally (i.p.)) or infused bilaterally into the hippocampus 15 min before gating measurements.
  
  
  RESULTS
  Systemic injection of CGP56999A, at a dose of 0.2 and 0.4 mg/kg i.p. resulted in reduced gating of hippocampal AEP in a dose-dependent manner. Reduced gating was found at conditioning-test interpulse intervals of 300-500 ms, but not 100-200 ms. Reduced gating of hippocampal AEP also followed bilateral infusion of CGP56999A into the hippocampus (0.1 μg/μL/side). Gating loss was attributed to a decreased conditioning response and an increased test response after systemic or local injection of CGP56999A. Robust PPI was found at prepulse-pulse intervals of 30-100 ms, and this PPI was reduced by hippocampal infusion of CGP56999A in a dose-dependent manner, as compared with saline infusion.
  
  
  CONCLUSIONS
  Blockade of hippocampal GABA(B) receptors led to deficits in sensory and sensorimotor gating, which are symptoms of schizophrenia.
authors.affiliation: Department of Physiology and Pharmacology, Medical Sciences Building, The University of Western Ontario, London, ON, Canada, N6A 5C1. jma2@uwo.ca
authors.forename: Jingyi
authors.initials: J
authors.lastname: Ma
authors.forename: L Stan
authors.initials: LS
authors.lastname: Leung
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001931:Brain Mapping; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D018080:Receptors, GABA-B / Q000378:metabolism*; D012565:Schizophrenic Psychology; D055139:Sensory Gating / Q000187:drug effects*
chemical_list: D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B