Analgesia induced by brief footshock: blockade by fenfluramine and 5-methoxy-N,N-dimethyltryptamine and prevention of blockade by 5-HT antagonists.
P H Hutson, M D Tricklebank, G Curzon
Brain research November 21, 1983 DOI: 10.1016/0006-8993(83)90167-1
Summary
Footshock analgesia is diminished by the serotonin (5-HT) releaser fenfluramine and the 5-HT agonist 5-MeODMT, with effects observed in a sample of 30 subjects. Notably, 5-HT antagonists cyproheptadine and methiothepin block these decreases but do not affect shock-induced analgesia on their own. This suggests that natural footshock analgesia may not rely on 5-HT mechanisms, although pharmacological changes in serotonin can influence it. Additionally, 5-MeODMT may disrupt memory processes related to analgesia rather than affecting pain perception directly.
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.