Combination of neonatal PolyI:C and adolescent phencyclidine treatments is required to induce behavioral abnormalities with overexpression of GLAST in adult mice.

Cumulative incidences of multiple risk factors are related to pathology of psychiatric disorders. The present study was designed to examine combinative effects of a neonatal immune challenge with adolescent abused substance treatment on the psychological behaviors and molecular expressions in the adult. C57BL/6J mice were neonatally treated, with polyriboinosinic-polyribocytidylic acid (PolyI:C: 5mg/kg) during postnatal days (PD) 2-6, then with phencyclidine (PCP: 10mg/kg) during adolescence (PD35-41). Locomotor activity was analyzed to evaluate sensitivity to PCP on PD35 and PD41. Emotional and cognitive tests were carried out on PD42-48. Neonatal PolyI:C treatment markedly enhanced sensitivity to PCP- and methamphetamine-induced hyperactivity in the adolescent. Mice treated with both neonatal PolyI:C and adolescent PCP (PolyI:C/PCP) showed social deficit and object recognition memory impairment. The expression of glutamate/aspartate transporter (GLAST) in the prefrontal cortex (PFC) was significantly increased in the (PolyI:C/PCP)-treated mice. Infusion of glutamate transporter inhibitor (DL-TBOA: 1 nmol/bilaterally) into the PFC reversed the object recognition impairment in the (PolyI:C/PCP)-treated mice. These results indicate that the combined treatment of neonatal PolyI:C with adolescent PCP leads to behavioral abnormalities, which were associated with increase of GLAST expression in the adult PFC.