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.

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 D(1)/D(2) 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 SDHxLEH cross, and subsequent offspring (N2) of an SDHxF1 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.