DANTROLENE SODIUM REVERSES THE INCREASE IN CAMP RESPONSE ELEMENT AND TPA RESPONSIVE ELEMENT DNA-BINDING ACTIVITY IN THE RABBIT BRAIN FOLLOWING HALOPERIDOL ADMINISTRATION AND HEAT-STRESS

Using electrophoretic mobility-shift assay (EMSA), we examined DNA-bin ding activity of cAMP response element (CKE), onto its responsive elem ent CKE, as well as TPA responsive element (TRE) in the medial hypotha lamus and striatum of the experimental rabbits administered with halop eridol under heat stress exposure and studied the effects of dantrolen e sodium to the transcriptional factor. In EMSA with nuclear extracts from the rabbit brain, the DNA-binding activities of CKE and TRE in me dial hypothalamus and striatum increased following haloperidol and hea t stress. These increases were maintained by coadministration with atr opine. The treatment with dantrolene sodium markedly reversed such inc reases. The alterations of activities of these transcriptional factors may reflect the therapeutic effect of dantrolene sodium.