Rats do not experience cortical or hippocampal spreading depression as aversive.

Cortical spreading depression (SD) may produce some symptoms of the aura of classical migraine but it is less probable that it can account for the headache. The aversiveness of SD was examined in unanesthetized rats. In Exp. 1, rats with implanted cortical cannulae were confined in the dark compartment of the step-through apparatus and repeated waves of SD were elicited in one hemisphere. After two such training sessions the rats did not evince passive avoidance of the compartment associated with cortical SD. In Exp. 2, thirsty rats with implanted hippocampal electrodes were trained to drink from two different spouts A and B. Hippocampal SD was elicited when the animal was drinking from spout A but not from spout B. Drinking was interrupted shortly after appearance of the SD wave and gradually recovered over the subsequent 10 min, but up to ten spout A-SD pairings did not change the animal's preference for spout A. It is concluded that cortical or hippocampal SD has no immediate or delayed aversive consequences.