D-ala2-Metenkephalinamide blocks the synaptically elicited cortical spreading depression in rats

Spreading depression (SD) was elicited in rats anesthetized with pentobarbital by a train of 8 electrical pulses (0.1 ms, 10 Hz) applied to parietal cortex. Local application of 50 micrograms of D-ala2-metenkephalinamide (DAME) on the stimulated area evoked one or two SD waves followed by an increase of SD threshold from 40 V to 90 V. This effect could be partly prevented by naloxone (1 mg/kg i.p.) and reversed by local application of 4-aminopyridine (10(-3) M, 2 microliters), which reduced SD threshold to 5 and 20 V in normal and DAME-treated cortex, respectively. It is argued that DAME exerts an inhibitory effect on cortical neurons and that the initial SD facilitation is due to initial blockade of inhibitory neurons in the superficial cortical layers.