Retigabine activates inward potassium rectifying KCNQ channels. This stabilizes the membrane potential via hyperpolarization in vitro and retigabine has also been shown to inhibit convulsions in vivo. This study was carried out to determine whether retigabine inhibited haloperidol-dependent activation of neurons in the striatum as measured by expression of c-Fos. Groups of male rats were treated with retigabine (10 mg/kg i.p.), haloperidol (1 mg/kg i.p.), or the two in combination (at 15 min interval) and fixed 60 min after haloperidol treatment. Haloperidol produced a large increase in the number of c-Fos-positive nuclei in different degrees in all parts of the striatum. Pretreatment with retigabine completely blocked haloperidol-induced c-Fos in both the ventral and dorsal striatum suggesting that retigabine via activation of the KCNQ channel interacts with haloperidol and inhibits neuronal excitation in the striatum.
Copyright 2004 Elsevier Ireland Ltd.