Increased GABAA receptor binding in amygdala after prenatal administration of valproic acid to rats

Objective: Prenatal exposure to valproic acid (VPA) enhances the risk for later development of autism spectrum disorders (ASD). An altered gamma-aminobutyric acid (GABA) system may be a key factor in ASD. Here we investigated possible changes in the GABA system in rats exposed to a low dose of prenatal VPA. Method: We performed autoradiography with [H-3] muscimol, (a GABA(A) receptor agonist), and [C-11]Ro15-4513 (a partial agonist of the GABA(A) alpha(1+5) receptor subtypes), in brain sections containing amygdala, thalamus and hippocampus of rats treated prenatally with 20 mg/kg VPA or saline from the 12th day of gestation. Result: Prenatal VPA significantly increased [C-11]Ro15-4513 binding in the left amygdala compared with controls (p < 0.05). This difference was not observed in the hippocampus, thalamus or right amygdala. No differences were observed in [H-3] muscimol binding. Conclusion: We observed an asymmetric increase in GABAA receptor binding. Disturbances in the GABAA receptor system have also been detected in human autism with [C-11]Ro15-4513.