Hyperthermia-enhanced serotonin (5-HT) depletion resulting from D-fenfluramine exposure is preventable.

Recent findings intricate that elevations in body temperature during acute d-fenfluramine (Fen) exposure enhance long-term 5-HT depletion. Therefore, we hypothesized that when repeated exposure to d-Fen produced repeated elev ations in body temperature, 5-HT reductions would be greater in comparison to a single d-Fen exposure. Groups of animals were exposed to d-Fen for 1 o r 4 days in a 28 degrees C environment. Exposure to d-Fen in the 28 degrees C environment induced an increase in body temperature and resulted in a lo ng-term decrease in brain 5-HT. However, brain 5-HT was not different betwe en the two groups. An additional experiment revealed that if the initial ex posure to d-Fen does not induce elevations in body temperature, then long-t erm 5-HT depletion can be prevented. We conclude that the central nervous s ystem rapidly adapts to the 5-HT depleting action of d-Fen thereby preventi ng further decreases in 5-HT concentrations from d-Fen exposure. In additio n, this rapid adaptation circumvented the hyperthermia-enhanced 5-HT deplet ion that results from d-Fen exposure in a warm environment.