GABA(B) receptor blockade in the hippocampus affects sensory and sensorimotor gating in Long-Evans rats.

RATIONALE: Sensory and sensorimotor gating deficits are observed in schizophrenia. GABA(B) receptor deficiency is also detected in the hippocampus of schizophrenic patients. OBJECTIVES: 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