Abstract
Sensorimotor gating, measured by prepulse inhibition (PPI) of the startle reflex, is reduced in schizophrenia patients and in rats treated with dopamine agonists. Strain and substrain differences in the sensitivity to the PPI-disruptive effects of dopamine agonists may provide insight into the genetic basis for human population differences in sensorimotor gating. We have reported greater sensitivity to the PPI-disruptive effects of the D1/D2 agonist apomorphine in Harlan Sprague–Dawley (SDH) vs Wistar (WH) rats. In the present study, we assessed the inheritance pattern of this phenotypic difference. Sensitivity to the PPI-disruptive effects of apomorphine was compared across parental SDH and WH strains, offspring (F1) of an SDH×WH cross, and subsequent offspring (N2) of an SDH×F1 cross. Apomorphine sensitivity followed a gradient of SDH>N2>F1>WH. Parental SDH and WH strains exhibited comparable sensitivity to the PPI-disruptive effects of phencyclidine. The nature of this gradient of APO sensitivity suggests relatively simple additive effects of multiple genes on the phenotype of PPI sensitivity.
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Acknowledgements
This research was supported in part by grants from the National Institute of Mental Health (MH-01436, MH-53484, MH-42228) and the Department of Veterans Affairs VISN 22 Mental Illness Research, Education and Clinical Centers (MIRECC).
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Swerdlow, N., Platten, A., Hanlon, F. et al. Sensitivity to Sensorimotor Gating-Disruptive Effects of Apomorphine in two Outbred Parental Rat Strains and their F1 and N2 Progeny. Neuropsychopharmacol 28, 226–234 (2003). https://doi.org/10.1038/sj.npp.1300035
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DOI: https://doi.org/10.1038/sj.npp.1300035
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