Magnesium valproate attenuates hyperactivity induced by dexamphetamine-chlordiazepoxide mixture in rodents

A mixture of dexamphetamine and chlordiazepoxide induces hyperactivity in both mice and rats. This type of hyperactivity has been proposed as an animal model of mania. Magnesium valproate itself had little influence on the activity of normal mice and rats. Acute pretreatment of mice with magnesium valproate (75-300 mg/kg p.o., 37.5-150 mg/kg i.v.) attenuated the mixture-induced hyperactivity. Pretreatment of rats with a single dose of magnesium valproate (75-300 mg/kg, p.o. or i.p.) also counteracted the locomotor hyperactivity caused by the mixture. The effects of magnesium valproate in the mixture-treated mice and rats could be abolished by bicuculline and picrotoxin, but not isoniazid. These findings suggest that the antimanic effect of valproate may be related to its ability to enhance the postsynaptic effects of gamma-aminobutyric acid (GABA).