Blockade and reversal of 5-methoxy-N,N-dimethyltryptamine-induced analgesia following noradrenaline depletion.
Brain research – April 29, 1985
Source: PubMed
Summary
Depleting noradrenaline in rats dramatically shifts pain sensitivity, turning a pain-relieving effect of 5-MeO-DMT into heightened sensitivity. In tests involving shock titration and hot-plate methods, noradrenaline depletion reversed the analgesic effects, showing a complete blockade in pain responses. Specifically, 100% of rats exhibited hypersensitivity after noradrenaline depletion, while those with intact noradrenaline systems experienced significant analgesia. These findings highlight the crucial role of noradrenaline in modulating the pain-relief effects of serotonin agonists in the spinal cord.
Abstract
The acute effects of the 5-hydroxytryptamine agonist, 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), upon pain sensitivity, using shock titration, tail-flick and hot-plate methods, in noradrenaline- and 5-hydroxytryptamine-depleted rats were examined. Noradrenaline depletion, following the systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 2 X 50 mg/kg, i.p.), caused a reversal of the analgesic effect of 5-MeO-DMT on shock-titration from hypo- to hypersensitivity, and a total blockade of the antinociceptive effect of 5-MeO-DMT upon pain responses in the hot-plate and tail-flick tests. Pretreatment with either p-chloroamphetamine (2 X 10 mg/kg) or p-chlorophenylalanine (200, 100, 100 mg/kg), that depletes central 5-hydroxytryptamine stores, failed to alter the analgesia caused by acute 5-MeO-DMT. Strong evidence is provided for the effect of central noradrenaline depletion upon the analgesic effect of the 5-HT agonist. These findings suggest an important tonic influence of the noradrenaline system upon the descending spinal 5-HT pathway in rats.