The effect of discontinuing dehydroepiandrosterone supplementation on Zucker rat food intake and hypothalamic neurotransmitters
Porter, J.R.; Abadie, J.M.; Wright, B.E.; Browne, E.S.; Svec, F.
International Journal of Obesity and Related Metabolic Disorders Journal of the International Association for the Study of Obesity 19(7): 480-488
1995
ISSN/ISBN: 0307-0565 PMID: 8520638 Document Number: 454572
OBJECTIVE: Dehydroepiandrosterone (DHEA) decreases body weight and food intake of the obese Zucker rat, a model of youth-onset obesity associated with hyperphagia. The effects of discontinuing DHEA treatment on these parameters, however, has not been investigated. This question was studied in rats that had been maintained on DHEA-supplemented (0.0%, 0.06%, 0.15%, 0.3% or 0.6%) diets for 7 days. METHOD: The results were correlated with regional levels of hypothalamic neurotransmitters in rats treated with 0.6% DHEA for 7 days in a separate experiment. Neurotransmitter changes were evaluated after Day 0 (7 days of treatment), and Day +1 and Day +2 post-DHEA. RESULTS: Upon removing dietary DHEA, rats immediately (+1 day) consumed significantly more food than while on the DHEA-supplemented diet. Indeed, they consumed even more food than the group that had always been on the DHEA-free diet. This intake above control lasted for as long as +9 days post-DHEA treatment. After 7 days of DHEA treatment, lateral hypothalamic (LH) serotonin (5-HT) and dopamine (Dpm) were elevated significantly (P lt 0.05) compared to untreated controls. Norepinephrine, and 5-HIAA were not significantly different from control. These immediate changes in 5-HT and Dpm returned to baseline by day 2 of post-DHEA treatment. No significant changes occurred in either the ventromedial hypothalamus (VMH) or the paraventricular nucleus (PVN). CONCLUSIONS: These observations suggest that there is a possible relationship between increases of LH 5-HT and Dpm with 0.6% DHEA treatment. Both are inhibitory to food intake and DHEA at the 0.6% dose causes hypophagia after 7 days of treatment (i.e. 0 days). Subsequent decreases of these monoamines occurred during the post-DHEA period at both +1 and +2 days. Return of these inhibitory monoamines to baseline could be responsible for reversal of the hypophagia, however, they do not rule out the production of a separate stimulator of food intake.