O-5-9 - Factors affecting melatonin sensitivity to light: Relevance for a putative marker of bipolar affective disorder

Abstract

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 effect of either drug, although two studies have hinted at increased adrenal activity. There are also considerable differences in the literature pertaining to the neurotoxic effects of d,l- and d-FEN. Some possible explanations for these differences include: activation of different neurotransmitter systems, the temperature at which the animals were maintained during exposure, or the substance sampled in each study. We investigated the effects of either 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 produce elevations in glial fibrillary acidic protein (GFAP) under hyperthermic conditions, we examined the effects of d- and d,l-FEN (15 mg/kg, four times) on GFAP content when the animals were dosed at ambient temperatures of 21 or 32°C. Approximately fivefold increases of corticosterone and threefold increases of aldosterone were found 72 h later under resting conditions following both d- and d,l-FEN. Nonetheless, when animals were dosed with d-FEN at 32°C, no significant elevation in corticosterone was detected. No effect was observed for ACTH, testosterone, or GFAP following d- or d,l-FEN treatment. These data suggest that: (1) FEN treatment causes prolonged elevations in adrenal cortical hormones; (2) FEN-treated animals displayed hormonal characteristics similar to animals undergoing a chronic stressor as suggested by no difference in ACTH titers; (3) d,l-FEN treatment or d-FEN treatment (as reported previously) is not similar to other substituted amphetamines in that it does not increase GFAP, even under hyperthermic conditions.