@article {Stewart1144, author = {Christopher W. Stewart and John F. Bowyer and William Slikker, Jr.}, title = {Elevated Environmental Temperatures Can Induce Hyperthermia During d-Fenfluramine Exposure and Enhance 5-Hydroxytryptamine (5-HT) Depletion in the Brain}, volume = {283}, number = {3}, pages = {1144--1150}, year = {1997}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {d-Fenfluramine (d-Fen) has been demonstrated to alter body temperature (BT), decrease 5-hydroxytryptamine (5-HT) and decrease 5-HT plasma membrane transporters (PMT) in rats. Therefore, experiments were designed to test whether a correlation existed between elevated BT and brain 5-HT depletions. It was hypothesized thatd-Fen would induce hyperthermia if the environmental temperature was elevated. Experiments were conducted to determine 1) the dose-response of d-Fen on BT in a 28{\textdegree}C environment, 2) the acute effect of d-Fen on long-term depletion of 5-HT and 5-HT PMT in a 4{\textdegree}C, 22{\textdegree}C or 28{\textdegree}C environment and 3) the effect of a 22{\textdegree}C environment vs. a 28{\textdegree}C environment on the plasma levels of d-Fen and d-norfenfluramine.d-Fen produced a dose-dependent elevation of BT in the 28{\textdegree}C environment, decreased BT in the 4{\textdegree}C environment and had no effect on BT in the 22{\textdegree}C environment. Exposure to d-Fen in the 4{\textdegree}C or 22{\textdegree}C environment reduced 5-HT and 5-HT PMT concentrations compared with control. However, greater reductions of 5-HT and 5-HT PMT concentrations occurred in the 28{\textdegree}C environment. Conversely, the plasma levels of d-Fen andd-norfenfluramine were not altered. Thus these experiments demonstrate that increased BT during d-Fen exposure occurs at elevated environmental temperatures without altering the plasma concentrations of the drug and results in an enhanced long-term depletion of brain 5-HT and 5-HT PMT. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/283/3/1144}, eprint = {https://jpet.aspetjournals.org/content/283/3/1144.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }