title: Alterations to prepulse inhibition magnitude and latency in adult rats following neonatal treatment with domoic acid and social isolation rearing.
abstract: Deficits in perceptual, informational, and attentional processing are consistently identified as a core feature in schizophrenia and related neuropsychiatric disorders. Neonatal injections of low doses of the AMPA/kainate agonist domoic acid (DOM) have previously been shown to alter various aspects of perceptual and attentional processing in adult rats. The current study investigated the effects of combined neonatal DOM treatment with isolation rearing on prepulse inhibition behaviour and relevant neurochemical measures, to assess the usefulness of these paradigms in modeling neurodevelopmental disorders. Daily subcutaneous injections of DOM (20 μg/kg) or saline were administered to male and female rat pups from postnatal days (PND) 8-14. After weaning, rats were either housed alone or in groups of 4. Both the magnitude and latency of prepulse inhibition were determined in adulthood (approximately 4.5 months of age) and post-mortem brain tissue was assayed using Western blot. Social isolation alone significantly lowered PPI magnitude in male (but not female) rats while DOM treatment appeared to make animals refractory to this effect. Combining social isolation and DOM treatment caused an additive decrease in PPI startle latency. No statistically significant differences were found in the expression of D1, D2, TH, GAD65 or GAD67 protein in either the prefrontal cortex or hippocampus, although some tendencies toward differences were noted. We conclude that both neonatal low-dose DOM and social isolation affect prepulse inhibition in rats but that each paradigm exerts these effects through different neuronal signalling systems.
authors.affiliation: Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Marriott
authors.affiliation: Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, PE, Canada. Electronic address: tasker@upei.ca.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Tasker
authors.affiliation: Department of Psychology, University of Prince Edward Island, Charlottetown, PE, Canada.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Ryan
authors.affiliation: Department of Psychology, University of Prince Edward Island, Charlottetown, PE, Canada.
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Doucette
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology; D012934:Social Isolation / Q000523:psychology
chemical_list: C012301:domoic acid; D007608:Kainic Acid
keywords: Animal models; Domoic acid; Isolation rearing; Neurodevelopmental disorders; Prepulse inhibition; Schizophrenia