Cholinergic overstimulation supports conditioned-facilitated startle but not conditioned hyperalgesia

Pyridostigmine bromide (PB), a peripheral cholinesterase inhibitor, has been shown to support odor-potentiated startle responding in rats. Here we conducted 2 sets of experiments that further characterize aspects of this learned association. First we conducted experiments designed to further characterize the learning parameters of the odor-PB association that leads to startle facilitation weeks later. We found that an acute injection of PB causes an increase in startle reactivity that lasts less than 2 h. This is evidence for PB's direct action on the startle response as an enhancing agent. We also delineated the duration of the conditioned enhancement to less than 4 weeks. Second, we conducted similar studies but substituted a nociceptive paw-lick response (thermal pain reflex) for the startle reflex. PB did not have an unconditional action upon the latency to paw-lick to a 48.5 °C heated plate nor did any subsequent changes in paw-lick occur in the presence of the previously paired odor. These results suggest that the actions of PB, as an unconditional stimulus, are limited to specific behaviors. Future work examining this compound as a source of conditioned symptoms (as in the case of Gulf War Illness) should focus on those symptoms that are directly influenced by peripheral cholinergic activity.