Cortical spreading depression-associated cerebral blood flow changes induced by mechanical stimulation are modulated by AMPA and GABA receptors.

Migraine is one of the most prevalent neurological disorders with some 30% of patients additionally suffering from focal neurological disturbances: the aura. The underlying mechanism behind the aura is generally considered to be a form of cortical spreading depression (CSD). We used mechanical stimulation to induce hyperaemia associated with CSD in cats and rats, and studied the effect of a glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor, antagonist, and gamma-aminobutyric acid (GABA)(A) and GABA(B) receptor agonists, to understand better the pharmacology of CSD. All three were able to inhibit CSD-associated cerebral blood flow changes in the rat and in a proportion of cats studied; non-responders showed altered speed of propagation and time to induction. The data suggest AMPA and GABA receptors may be targets of migraine therapy in inhibiting CSD and thus may alter the frequency of migraine aura.