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Am J Physiol Regul Integr Comp Physiol 288: R928-R935, 2005; doi:10.1152/ajpregu.00290.2003
0363-6119/05 $8.00
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

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

Johnny Porter,1 Michael Van Vrancken,1 Connie Corll,1 Hilary Thompson,2 and Frank Svec3

Obesity Research Program, Center of Excellence in Oral Biology, Departments of 3Medicine, 1Physiology and Ophthalmology, 2LSU Eye Center, Louisiana State University, Health Sciences Center, New Orleans, Louisiana

Submitted 28 May 2003 ; accepted in final form 2 December 2004

The 5 HT1A 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-HT1A 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.

obesity; dehydryoepiandrosterone; calorie intake; monoamine



Address for reprint requests and other correspondence: J. R. Porter, Department of Physiology, Louisiana State Univ., 1100 Florida Ave., New Orleans LA, 70119 (E-mail: physjrp{at}lsuhsc.edu)







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