Sensitivity to the dopaminergic regulation of prepulse inhibition in rats:Evidence for genetic, but not environmental determinants

Prepulse inhibition (PPI), a measure of sensorimotor gating, is reduced in schizophrenia patients and in rats treated with dopamine (DA) agonists. Rep orted strain and supplier-based differences in sensitivity to PPI-disruptiv e effects of DA agonists presumably reflect the differential impact of gene tics and/or environment on DAergic substrates regulating PPI. In 2000, Harl an Laboratories established a Texas Sprague-Dawley line (SDHt; facility 211 ) using breeders from Indianapolis (SDHi; facility 202A). SDHi rats had bee n used, approximately 11 years earlier, to establish a colony in San Diego (SDHsd; facility 235). SDHt and SDHi rats are thus genetically similar, but raised in distinct environments; approximately 11 years of genetic "drift" separates SDHsd rats from both SDHi and SDHt rats. Harlan Long-Evans hoode d rats (LEH; Madison, WI, facility 207) are genetically distinct from albin o SDH. All except SDHsd rats were shipped to our facility by air freight. W e used SDHt, SDHi, SDHsd, and LEH rats to assess genetic and environmental contributions to the DAergic regulation of PPI. Acoustic startle/PPI were a ssessed in rats treated with the D1/D2 agonist apomorphine (APO), the D2 ag onist quinpirole, or the D1 agonist SKF 82958. The relative sensitivities t o the PPI-disruptive effects were: APO: SDHt=SDHsd=SDHi>>LEH; SKF 82958: SD Ht = SDHsd = SDHi (LEH not sensitive); quinpirole: SDHt = SDHsd = SDHi; SDH i > LEH. Strain/supplier differences in sensitivity to drug effects on star tle magnitude did not correspond to patterns of PPI sensitivity. In these r ats, strain differences in the DAergic regulation of PPI are most easily ex plained by genetic, rather than environmental influences that differentiall y impact both D1 and D2 substrates. This finding is consistent with publish ed reports in other strains. Pharmacogenetic studies of PPI in rats may ide ntify a genetic basis for a model of deficient sensorimotor gating in schiz ophrenia. (C) 2001 Elsevier Science Inc. All rights reserved.