Elevations in plasmatic titers of corticosterone and aldosterone, in the absence of changes in ACTH, testosterone, or glial fibrillary acidic protein, 72 h following D,L-fenfluramine or D-fenfluramine administration to rats

Studies in both humans and animals demonstrate that D,L- and D-fenfluramine (D,L-FEN and D-FEN, respectively) can activate the hypothalamic-pituitary- adrenal axis following an acute dose. No data exist showing a prolonged eff ect of either drug, although two studies have hinted at increased adrenal a ctivity. There are also considerable differences in the literature pertaini ng to the neurotoxic effects of D,L- and D-FEN. Some possible explanations for these differences include: activation of different neurotransmitter sys tems, the temperature at which the animals were maintained during exposure, or the substance sampled in each study. We investigated the effects of eit her D,L-FEN or D-FEN on pituitary, adrenal, and gonadal hormones 72 h after drug exposure. Furthermore, using a dosing regimen adapted from studies on methamphetamine (e.g., four times every 2 h in a single day) known to prod uce elevations in glial fibrillary acidic protein (GFAP) under hyperthermic conditions, we examined the effects of D- and D,L-FEN (15 mg/kg, four time s) on GFAP content when the animals were dosed at ambient temperatures of 2 1 or 32 degreesC. Approximately fivefold increases of corticosterone and th reefold increases of aldosterone were found 72 h later under resting condit ions following both D- and D,L-FEN. Nonetheless, when animals were dosed wi th D-FEN at 32 degreesC, no significant elevation in corticosterone was det ected. No effect was observed for ACTH, testosterone, or GFAP following D- or D,L-FEN treatment. These data suggest that: (1) FEN treatment causes pro longed elevations in adrenal cortical hormones; (2) FEN-treated animals dis played hormonal characteristics similar to animals undergoing a chronic str essor as suggested by no difference in ACTH titers; (3) D,L-FEN treatment o r D-FEN treatment (as reported previously) is not similar to other substitu ted amphetamines in that it does not increase GFAP, even under hyperthermic conditions. (C) 2001 Elsevier Science Inc. All rights reserved.