THE EFFECT OF DISCONTINUING DEHYDROEPIANDROSTERONE SUPPLEMENTATION ONZUCKER RAT FOOD-INTAKE AND HYPOTHALAMIC NEUROTRANSMITTERS

OBJECTIVE: Dehydroepiandrosterone (DHEA) decreases body weight and foo d intake of the obese Zucker rat, a model of youth-onset obesity assoc iated with hyperphagia, The effects of discontinuing DHEA treatment on these parameters, however, has not been investigated, This question w as 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 we re correlated with regional levels of hypothalamic neurotransmitters i n rats treated with 0.6% DHEA for 7 days in a separate experiment. Neu rotransmitter 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 th an the group that had always been on the DHEA-free diet. This intake a bove control lasted for as long as +9 days post-DHEA treatment. After 7 days of DHEA treatment, lateral hypothalamic (LH) serotonin (5-HT) a nd dopamine (Dpm) were elevated significantly (P < 0.05) compared to u ntreated controls. Norepinephrine, and 5-HIAA were not significantly d ifferent from control, These immediate changes in 5-HT and Dpm returne d to baseline by day 2 of post-DHEA treatment, No significant changes occurred in either the ventromedial hypothalamus (VMH) or the paravent ricular nucleus (PVN). CONCLUSIONS: These observations suggest that th ere is a possible relationship between increases of LH 5-HT and Dpm wi th 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 day s). Subsequent decreases of these monoamines occurred during the post- DHEA period at both +1 and +2 days, Return of these inhibitory monoami nes to baseline could be responsible for reversal of the hypophagia, h owever, they do not rule out the production of a separate stimulator o f food intake.