The influence of dehydroepiandrosterone and 8-OH-DPAT on the caloric intake and hypothalamic neurotransmitters of lean and obese Zucker rats

Abstract

The 5 HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetraline (8-OH-DPAT) increases the food intake of satiated Zucker rats, both lean and obese. Associated with this increased intake are changes in the hypothalamic content of serotonin and its metabolite, 5-HIAA (5-hydroxyindole-3-acetic acid); serotonin is increased while the level of 5-HIAA is decreased. Analysis of individual 5-HIAA/5-hydroxytryptamine (5-HT) ratios, a measure of serotonin turnover indicate that 8-OH DPAT affected serotonin turnover equally and dramatically in both phenotypes. This would be an expected physiological action of an autofeedback mechanism by a 5-HT(1A) receptor agonist. Dehydroepiandrosterone (DHEA) at doses as low as 10 mg/kg blocks the 8-OH-DPAT-induced increase in food intake but does not alter food intake of control satiated Zucker rats. The mechanism of DHEA's action was investigated by monitoring the steroid's effect on hypothalamic neurotransmitters in this satiated model. DHEA by itself induced some change in 5-HIAA in the obese satiated model but not the lean. 8-OH-DPAT, by itself, dramatically decreased serotonin turnover in either lean or obese rats, and DHEA combined with 8-OH-DPAT did not further change serotonin turnover, suggesting DHEA may work through mechanisms other than monoamines to cause its inhibition of 8-OH-DPAT-induced behavioral effects at such low doses.

The neurosteroid dehydroepiandrosterone sulfate, but not androsterone, enhances the antidepressant effect of cocaine examined in the forced swim test — Possible role of serotonergic neurotransmission

“…influence on serotonin neurotransmission depends on the examined brain structure, but it does not seem to be dose-dependant, as similar results were obtained by groups using DHEA at doses 20 mg/kg (Porter et al, 2005) and 200 mg/kg (Nguyen et al, 1999).…”

Appetite and Endocrine Regulators of Energy Balance After 2 Days of Energy Restriction: Insulin, Leptin, Ghrelin, and DHEA‐S

“…Animal studies have consistently demonstrated reduced energy intake and weight loss due to exogenous DHEA‐S administration (42,44,45). In animals, these effects are dose‐dependent (41), differ between fatty phenotypes (42,43,47), and are attributed to appetite suppression from DHEA‐S acting via the central nervous system (48,49). In the present investigation, DHEA‐S was significantly higher during energy deprivation compared to energy balance.…”

Dehydroepiandrosterone (DHEA) blocks the increase in food intake caused by neuropeptide Y (NPY) in the Zucker rat

“…We then assayed brain tissue to determine the role of hypothalamic and raphe monoamines. We hypothesize that DHEA will interfere with the orexigenic effects of NPY correspondingly to our recent study with 8-OH DPAT (Porter et al 2005) and that this effect will be mediated, at least in part, via hypothalamic monoamines.…”

“…Given the previous hypothesis, blocking the serotonin system locally in the VMH should inhibit the ability of DHEA to reverse the behavioural effects of NPY on food intake. This step is crucial given that in a similar study DHEA blocked the increase in food intake caused via 8-OH DPAT (Porter et al 2005); an agent proposed to lower serotonin release (Zifa and Fillion 1992) and activates the 5-HT 1A receptor (Gilbert et al 1988;Hutson et al 1998;Zifa and Fillion 1992). The contradiction arises in that while DPAT lowered serotonin turnover, DHEA failed to raise serotonin turnover levels back to control despite having a behavioural effect (Porter et al 2005).…”