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Cortical spreading depression (CSD) has been implicated in migraine and as a headache trigger and can be evoked in experimental animals by electrical or chemical stimulation. We hypothesized that migraine prophylactic agents suppress CSD as a common mechanism of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:styled-content>\n                        <jats:italic>Methods<\/jats:italic>\n                      <\/jats:styled-content>\n                    <\/jats:title>\n                    <jats:p>\n                      Rats were treated either acutely or chronically over weeks and months, with one of the above migraine prophylactic drugs, vehicle, or\n                      <jats:sc>D<\/jats:sc>\n                      \u2010propranolol, a clinically ineffective drug. The impact of treatment was determined on the frequency of evoked CSDs after topical potassium application or on the incremental cathodal stimulation threshold to evoke CSD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:styled-content>\n                        <jats:italic>Results<\/jats:italic>\n                      <\/jats:styled-content>\n                    <\/jats:title>\n                    <jats:p>\n                      Chronic daily administration of migraine prophylactic drugs dose\u2010dependently suppressed CSD frequency by 40 to 80% and increased the cathodal stimulation threshold, whereas acute treatment was ineffective. Longer treatment durations produced stronger CSD suppression. Chronic\n                      <jats:sc>D<\/jats:sc>\n                      \u2010propranolol treatment did not differ from saline control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:styled-content>\n                        <jats:italic>Interpretation<\/jats:italic>\n                      <\/jats:styled-content>\n                    <\/jats:title>\n                    <jats:p>Our data suggest that CSD provides a common therapeutic target for widely prescribed migraine prophylactic drugs. Assessing CSD threshold may prove useful for developing new prophylactic drugs and improving upon existing ones. 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