The KCNQ channel activator retigabine blocks haloperidol-induced c-Fos expression in the striatum of the rat.
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.
Mikkelsen
Jens D
JD
Department of Molecular Physiology and Anatomy, NeuroSearch A/S, Pederstrupvej 93, 2750 Ballerup, Denmark. jdm@neurosearch.dk
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology*; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008297:Male; D010655:Phenylenediamines / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*; D024642:Potassium Channels, Voltage-Gated; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000927:Anticonvulsants; D002219:Carbamates; D018492:Dopamine Antagonists; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496911:Kcnq1 protein, rat; D010655:Phenylenediamines; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D016760:Proto-Oncogene Proteins c-fos; C101866:ezogabine; D006220:Haloperidol