SENSORIMOTOR GATING IN RATS IS REGULATED BY DIFFERENT DOPAMINE-GLUTAMATE INTERACTIONS IN THE NUCLEUS-ACCUMBENS CORE AND SHELL SUBREGIONS

The amplitude of the acoustic startle reflex is normally reduced when the startling stimulus is preceded by a weak click or 'prepulse'. Prep ulse inhibition (PPI) of acoustic startle has been used as an operatio nal measure of sensorimotor gating or inhibition, and is reduced in sc hizophrenia patients and in rats with central dopamine (DA) activation . The DA agonist-induced disruption of PPT in rats may thus offer a us eful animal model to study impaired sensorimotor gating in schizophren ia. We have previously reported that DA-glutamate interactions in the nucleus accumbens (NAC) regulate PPI. The NAC has at least two major s ubregions - the core and shell - that have distinct anatomical and neu rochemical properties. In this study. we compared changes in PPI after manipulations of DA-glutamate activity in these two NAC subregions. C onsistent with previous findings, infusion of the non-NMDA agonist AMP A into the NAC core subregion significantly reduced PPI, and this effe ct was opposed by systemic administration of the D-2 antagonist halope ridol. Also consistent with previous reports, infusion of the non-NMDA antagonist CNQX into the NAC core subregion did not alter PPI, but it s co-infusion with D-amphetamine (AMPH) attenuated the AMPH-disruption of PPI. In contrast, while PPI was reduced after AMPA infusion into t he NAC shell subregion, this effect of AMPA could not be blocked by pr etreatment with haloperidol. Infusion of either AMPH or CNQX into the NAC shell subregion reduced PPI independently. The PPI-disruptive effe cts of intra-shell CNQX infusion were not blocked by haloperidol. The present results suggest striking differences between the NAC core and shell subregions in their neurochemical modulation of sensorimotor gat ing of acoustic startle in the rat.