Central effects of dehydroepiandrosterone in Zucker rats

To investigate whether dehydroepiandrosterone (DHEA), an adrenal/gonadal androgen, can act centrally to reduce energy intake in a model of genetic obesity, the Zucker fatty rat. To investigate a possible mechanism of action.

Two experiments were performed in lean and obese female Zucker rats. In the first experiment, 24 h following administration of i.p. DHEA (200 mg/kg), three hypothalamic regions [lateral hypothalamus (LH), ventromedial nucleus (VMH), and paraventricular nucleus (PVN)] were analyzed for monoamine neurotransmitter concentrations. In the second experiment, DHEA (50 micrograms) was administered by i.c.v. injection. Energy intake for the following day was measured.

In the first experiment, concentrations of norepinephrine (NE), epinephrine (EPI), dopamine (DA), serotonin (5HT), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured. Ratios of 5HT/5HIAA were calculated. In the second experiment, kilojoules consumed per 24 h were calculated.

All LH monoamines, and PVN DA, displayed lower concentrations in obese than lean control rats. DHEA treatment reversed these reductions in obese rats without affecting lean rats. DHEA increased VMH EPI in obese rats only. DHEA increased PVN NE in both lean and obese rats. I.C.V. DHEA decreased energy intake in obese but not lean rats.

The i.c.v. results suggest that DHEA exerts a phenotype specific, centrally mediated inhibitory effect on food intake. In addition, in doses previously shown to reduce energy intake in obese but not lean rats, i.p. DHEA reversed reduced concentrations of many monoamines, particularly in the LH, in obese animals only. These latter changes provide indirect evidence to suggest that these central neurotransmitters may play an important role in the antiobesity effect of DHEA in the Zucker fatty rat.