Drugs that increase serotonin activity—5-MeO-DMT, fenfluramine, and PCA—impair rats' ability to retain fear, as shown by reduced immobility after inescapable shocks. Long-term PCA treatment, which depletes central serotonin neurons, completely blocked the retention impairment caused by acute PCA and fenfluramine, and partially blocked the deficit from 5-MeO-DMT. However, serotonin depletion via PCPA did not block these effects, suggesting different serotonin stores are involved. These findings underscore the role of the ascending serotonin pathway in aversive conditioning in rats.
Repeated administration of drugs that increase tryptaminergic neurotransmission blocked the effects of an acute injection of 5-MeODMT on postdecapitation convulsions in rats. Zimelidine, fluoxetine, amiflamine, and alpha-ethyltryptamine given orally over 10 days substantially blocked the increase in latency and duration of convulsions caused by 5-MeODMT, while alaproclate, clorgyline, and pargyline caused a lesser blockade. Repeated 5-MeODMT administration completely blocked the acute effects. These findings suggest down-regulation of serotonin receptors mediating the convulsion response and offer a simple model for studying receptor sensitivity changes at the spinal level.