Chronic microinjection of valproic acid into the nucleus accumbens attenuates amphetamine-induced locomotor activity.

Amphetamine (AMPH)-induced hyper-locomotion has been well manifested in an animal model of psychiatric diseases such as drug addiction and bipolar disorder. In this study, we investigated the effects on AMPH-induced locomotor activity of chronically microinjected valproic acid into the nucleus accumbens (NAcc). Rats with guide cannular implanted bilaterally were divided into three groups and either saline or valproic acid (100 or 300 microg/0.5 microl/side) was microinjected into the NAcc once daily for 7 days. On day 8, half of each group received either saline or AMPH (1mg/kg, i.p.), respectively, and locomotor activity was measured for 2h. The increases of both horizontal locomotion and rearing by AMPH were attenuated in the rat pre-treated with valproic acid compared to saline in a dose-dependent manner. These results indicate that neuronal modifications in the NAcc induced by chronic valproic acid can modulate amphetamine-induced locomotor activity.