title: Heritable differences in the effects of amphetamine but not DOI on startle gating in albino and hooded outbred rat strains.
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 reported heritable differences in sensitivity to the PPI-disruptive effects of the D1/D2 agonist apomorphine (APO) in Harlan Sprague-Dawley (SDH) and Long-Evans (LEH) rats, offspring (F1) of an SDHxLEH cross, and subsequent offspring (N2) of an SDHxF1 cross. In this study, we assessed the neurochemical specificity of this heritable phenotype across parental SDH and LEH strains, and their F1 and N2 offspring, based on their sensitivity to the PPI-disruptive effects of the indirect DA agonist D-amphetamine (AMPH) and the 5HT2A agonist DOI. AMPH sensitivity followed a gradient of SDH>N2>F1>LEH, consistent with past findings with APO. DOI sensitivity did not differ across strains or generations. These findings demonstrate that the heritable phenotype in this model is not specific to a particular compound (APO), and reflects physiological differences in the DAergic, but not serotonergic, regulation of PPI.
authors.affiliation: Department of Psychiatry, 0804, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. nswerdlow@ucsd.edu
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: Jody M
authors.initials: JM
authors.lastname: Shoemaker
authors.forename: Amanda
authors.initials: A
authors.lastname: Platten
authors.forename: Leia
authors.initials: L
authors.lastname: Pitcher
authors.forename: Jana
authors.initials: J
authors.lastname: Goins
authors.forename: Sarah
authors.initials: S
authors.lastname: Crain
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D008297:Male; D010641:Phenotype; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000235:genetics*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D006213:Hallucinogens; D017366:Serotonin Receptor Agonists; D000661:Amphetamine; D001058:Apomorphine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine