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Heritable differences in the dopaminergic regulation of sensorimotor gating

I. Apomorphine effects on startle gating in albino and hooded outbred rat strains and their F1 and N2 progeny

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Abstract

Sensorimotor gating, measured by prepulse inhibition (PPI) of the startle reflex, is reduced in schizophrenia patients and in rats treated with dopamine (DA) agonists. Strain and substrain differences in the sensitivity to the PPI-disruptive effects of DA agonists may provide insight into the 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) versus Long Evans (LEH) rats. In the present study, we assessed the generational pattern of this phenotypic difference across parental SDH and LEH strains under in- and cross-fostering conditions, offspring (F1) of an SDH×LEH cross, and subsequent offspring (N2) of an SDH×F1 cross. Apomorphine sensitivity followed a gradient across generations that suggested relatively simple additive effects of multiple genes. Cross fostering studies confirmed that SDH>LEH apomorphine sensitivity did not reflect post-natal maternal influences. Generational patterns of PPI apomorphine sensitivity were not associated with albino versus hooded phenotypes per se, but apomorphine sensitivity in hooded N2 rats was strongly related to body surface area of fur pigmentation. The association between pigmentation and PPI apomorphine sensitivity may provide an important clue to specific biochemical and genetic substrates responsible for population differences in the regulation of sensorimotor gating.

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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). The authors are grateful for editorial comments provided by Dr. Robert Luedtke.

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Authors and Affiliations

  1. Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA

    Neal R. Swerdlow, Jody M. Shoemaker, Amanda Platten, Leia Pitcher, Jana Goins & Pamela P. Auerbach

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  1. Neal R. Swerdlow
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  2. Jody M. Shoemaker
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  3. Amanda Platten
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  4. Leia Pitcher
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  5. Jana Goins
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  6. Pamela P. Auerbach
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Correspondence to Neal R. Swerdlow.

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Swerdlow, N.R., Shoemaker, J.M., Platten, A. et al. Heritable differences in the dopaminergic regulation of sensorimotor gating. Psychopharmacology 174, 441–451 (2004). https://doi.org/10.1007/s00213-003-1481-3

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  • DOI: https://doi.org/10.1007/s00213-003-1481-3

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