Heritable differences in the effects of amphetamine but not DOI on startle gating in albino and hooded outbred rat strains.
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.
Swerdlow
Neal R
NR
Department of Psychiatry, 0804, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA. nswerdlow@ucsd.edu
Shoemaker
Jody M
JM
Platten
Amanda
A
Pitcher
Leia
L
Goins
Jana
J
Crain
Sarah
S
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
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