Fig. 1

Outline of experimental protocols. ASD-like symptoms were induced in Sprague-Dawley male and female rat offspring of dams that had received an intraperitoneal injection of valproic acid (VPA, 500 mg/kg) at gestational day 12.5 (G 12.5). Offspring were first checked for negative geotaxis and olfactory discrimination (tests of developmental milestones) and from postnatal day (PND) 21 to the end of the experimental procedures were fed with a standard diet (SD) or fenofibrate-enriched diet (FBR). After 4 weeks of treatment, animals were subjected to behavioral and/or neurochemical analysis. a From PND 48–53, the four experimental groups (each group n = 12) were behaviorally tested to evaluate the level of anxiety (elevated plus maze test), social interaction (three-chamber test), locomotor activity, and stereotypies. One week after the end of behavioral tests, animals were sacrificed and brain regions were dissected out for immunoblotting assays. b The four experimental groups (n = 12) of second cohort underwent behavioral screening to evaluate social transmission of food preference and perseverative behavior (marble burying test). In addition, animals were tested for the two-bottle sucrose preference as an index of hedonic response. One week later, animals were sacrificed and brain regions were dissected out for immunoblotting assays. c The third cohort was used to determine by immunoblotting the Thr³⁴ phosphorylation levels of DARPP-32 in response to social interaction or nonsocial stimulus (sucrose consumption) in the shell of NAc (NAcS). At PND 48–53, half animals in each group were sacrificed at baseline and half 30 min after a 10 min-interaction with a novel conspecific (social stimulus) or 30 min after consumption of 10 sucrose pellets. For each experimental group in this cohort, the rats not exposed to the social or sucrose stimulus were also used to assay the PPARα levels in the VTA