Autism-Inducing Prenatal VPA Treatment

VPA (Cayman Chemical, Ann Arbor, MI, USA) was dissolved in saline at a concentration of 250 mg ml⁻¹ and administered at a dose (500 mg kg⁻¹) and time (gestational day 12.5) that have been shown to induce autistic-like behavioral changes in the offspring.^{41 (link)}The anandamide hydrolysis inhibitor URB597 (Sigma-Aldrich, Milan, Italy) was dissolved in 5% Tween 80/5% polyethylene glycol/saline and administered intraperitoneally either 2 h (for the behavioral tests performed at adolescence and adulthood) or 30 min (for the behavioral tests performed at infancy) before testing. Drug dose and pre-treatment intervals were based on literature,^{29 (link), 35 (link), 37 (link), 38 (link), 42 (link)} and on pilot experiments. The solutions were administered in a volume of 2.5 ml kg⁻¹ at infancy, 2 ml kg⁻¹ at adolescence and 1 ml kg⁻¹ at adulthood.