Analgesia caused by a brief footshock in rats is reduced by drugs that increase serotonin (5-HT) activity—fenfluramine, which releases serotonin, and 5-MeODMT, a fast-acting serotonin agonist. These reductions are blocked by serotonin antagonists cyproheptadine and methiothepin, but those antagonists alone do not affect the shock-induced pain relief. Thus, the natural analgesia from brief footshock likely does not rely on serotonin mechanisms, though it can be altered by pharmacologically boosting serotonin. 5-MeODMT could also weaken analgesia after it starts, possibly by disrupting memory rather than pain processing directly.
Certain drugs, such as phencyclidine (PCP) and 8-OH-DPAT, disrupt prepulse inhibition (PPI) of the startle response in both Sprague Dawley and Wistar rats. However, apomorphine and amphetamine only disrupt PPI in Wistar rats, not in Sprague Dawley rats. This strain difference is specific to PPI, as apomorphine-induced hyperlocomotion, another measure of dopamine receptor activation, was similar in both strains. The findings suggest that the effects of dopamine receptor agonists on PPI can be dissociated from their effects on other behavioral models of dopamine activation.