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.
Department of Psychiatry, UCSD School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. nswerdlow@ucsd.edu
Neal R
NR
Swerdlow
Jody M
JM
Shoemaker
Amanda
A
Platten
Leia
L
Pitcher
Jana
J
Goins
Pamela P
PP
Auerbach
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001835:Body Weight / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005684:Gait / Q000187:drug effects* / Q000235:genetics; D007178:Inbreeding; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010375:Pedigree; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000235:genetics; D012880:Skin Pigmentation / Q000235:genetics; D013045:Species Specificity
D018491:Dopamine Agonists; D001058:Apomorphine; D004298:Dopamine