Ventral pallidal GABA-A receptors regulate prepulse inhibition of acoustic startle

Prepulse inhibition (PPI) of the acoustic startle reflex occurs when a weak auditory stimulus is presented 30-500 ms before the startling stimulus. Previous studies have shown that PPI is modulated by GABAergic projections from the ventral striatum to the ventral pallidum (VP). To evaluate the anatomical and pharmacological substrates of pallidal modulation of PPI, we measured PPI after intrapallidal infusion of GABA-B and GABA-A antagonists. Intrapallidal infusion of the GABA-B antagonist, 2-OH-saclofen (0.025-0.10 microgram), did not significantly alter PPI, startle amplitude or peak startle latency. Infusion of the GABA-A antagonist, picrotoxin (0.02-0.08 microgram), into the medial or central VP significantly reduced PPI; this effect appeared somewhat weaker after picrotoxin infusion into the lateral VP and was absent after infusion into the adjacent fundus striatum (FS). There was no significant effect of picrotoxin infusion into any of the VP sites or FS on startle amplitude or peak startle latency. Thus, ventral striato-pallidal GABAergic modulation of PPI appears to be mediated solely by GABA-A receptors and this modulatory substrate is predominantly distributed across the medial and central portions of the VP.