Analgesia induced by brief footshock: blockade by fenfluramine and 5-methoxy-N,N-dimethyltryptamine and prevention of blockade by 5-HT antagonists.

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.

Study at a glance

Abstract

Analgesia induced by footshock (2 mA, 30 s) is decreased by the 5-HT releaser, fenfluramine, and the rapidly acting 5-HT agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). These decreases are blocked by the 5-HT antagonists, cyproheptadine and methiothepin. However, the antagonists when given alone do not influence shock-induced analgesia. Therefore, analgesia induced by brief footshock in the absence of drugs may not involve 5-HT-dependent mechanisms even though it may be influenced by pharmacologically provoked changes of 5-HT release or by 5-MeODMT. This drug was also able to attenuate the analgesia after its induction, possibly reflecting a disruption of memory processes rather than of nociceptive mechanisms per se.