Does metoprolol inhibit the cortical spreading depression? Acute effects of systematic metropol on CSD in rats

Cortical spreading depression (CSD) is supposed to be the underlying biological basis of the migraine aura. Metoprolol was proven to be effective in migraine prophylaxis in clinical trials, but its mechanism of action has not been clarified yet. We studied direct effects of metoprolol on a continuous CSD induction model in rats. Six adult Wistar rats were anaesthetized with intraperitoneal thiopental (50 mg/kg). CSD was induced with application of 1 m KCL through a burr hole into the left frontal dura-mater, and recorded by an Ag/AgCl DC electrode on the left parietal dura-mater. After a basal recording of CSD induction during the first 40-min period, metoprolol (5 mg/kg) was infused within 4 min. Then DC recordings were maintained for a further 120 min. Any significant differences in total number and duration of CSDs before and after metoprolol administration were not detected. This study suggests that the mode of action of metoprolol in prophylaxis is not via direct CSD inhibition.