Enhanced locomotor activity in rats with excitotoxic lesions of the entorhinal cortex, a neurodevelopmental animal model of schizophrenia: behavioral and in vivo microdialysis studies

Abstract

In order to examine the construct validity of rats with excitotoxic damage of the left entorhinal cortex (EC) as an animal model of schizophrenia, we measured dopamine (DA)-related behaviors and methamphetamine (MAP)-induced DA release in the accumbens nucleus (NAC) in these animals. Quinolinic acid (lesion group) or phosphate buffer (sham group) was infused into the left EC of adolescent (postnatal 7 weeks) male Wistar rats. On the 14th and 28th postoperative day, spontaneous and MAP (1 mg/kg, i.p.)-induced locomotor activities, as well as MAP-induced stereotypy, were measured. The lesioned rats exhibited significantly greater spontaneous or MAP-induced locomotor activity on both of the postoperative days than did sham-operated animals, while EC lesions did not affect MAP-induced stereotypy on either occasion. MAP (1 mg/kg, i.p.)-induced DA release in NAC was measured by in vivo microdialysis on the 28th postoperative day. Lesioned rats did not show a significant change in MAP (1 mg/kg, i.p.)-induced DA release in NAC compared to sham-operated animals. These results suggest that excitotoxic damage of the left EC produces behavioral changes consistent with altered mesolimbic dopaminergic transmissions, possibly mediated by postsynaptic supersensitivity.