Auditory information processing in rat genotypes with different dopaminergic properties

Rationale: Auditory filtering disturbances, as measured in the sensory gati ng and prepulse inhibition (PPI) paradigms, have been linked to aberrant au ditory information processing and sensory overload in schizophrenic patient s. In both paradigms, the response to the second stimulus (S2) is attenuate d by an inhibitory effect of the first stimulus (S1). Dopamine (DA) agonist s have been found to reduce gating of auditory evoked potentials (AEPs) and PPI in healthy human subjects and in rats. These effects have been linked to DA hyperactivity in the mesolimbic system. A non-invasive approach in st udying the role of the DA system in PPI and AEP gating is to compare rat ge notypes that are marked by distinct DA systems. Objectives: Several questio ns were asked in the present study. Are PPI and AEP gating disturbed in (a) rats that are marked by a relatively high DA reactivity of the mesolimbic system, namely apomorphine-susceptible (APO-SUS) and WAG/Rij rats or in (b) rats that are marked by a relatively high DA activity of the nigrostriatal system, namely apomorphine-unsusceptible (APO-UNSUS) and ACI rats? Moreove r. is the particular DA balance (c) between the nigrostriatal and mesolimbi c system related to deficits in PPI and AEP gating? Methods: For this purpo se, the above-mentioned four rat genotypes (APO-SUS, APO-UNSUS, ACI and WAG /Rij) that vary in DA balance between both systems, were compared in the AE P gating paradigm. PPI was only measured in the ACI and WAG/Rij rats, since it has already been shown in a previous study that APO-SUS rats show dimin ished PPI as compared to rats of the APO-UNSUS genotype. Results: AEP gatin g of the vertex N50 was significantly reduced in WAG/Rij rats as compared t o the remaining three rat genotypes (APO-SUS, APO-UNSUS and ACI). No PPI de ficits were found in the ACI and WAG/Rij rats, although ACI rats had a sign ificantly higher basal startle amplitude. Conclusions: The PPI deficit in A PO-SUS and not in the other genotypes, suggests that especially a relativel y high DA reactivity of the mesolimbic system, together with a relatively l ow activity of the nigrostriatal system, contributes to this deficit. In co ntrast, the N50 gating deficit in WAG/Rij rats and not in the other genotyp es suggests that a relatively high DA activity of the nigrostriatal system together with a relatively high DA reactivity of the mesolimbic system is n ecessary for the presence of a N50 gating deficit. On the basis of these re sults we have concluded that both auditory filtering processes are differen tly regulated by DA in the nigrostriatal and mesolimbic systems.