title: Exaggerated feedback control decreases brain serotonin concentration and elicits hyperactivity in a rat model of diet-restriction-induced anorexia nervosa.
abstract: 5-Hydroxytryptamine (5-HT; serotonin) system is the major neurotransmitter system of interest in research on anorexia nervosa (AN). The AN patients show extreme dieting weight loss, hyperactivity and low basal levels of 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of 5-HT in the cerebrospinal fluid (CSF). Studies on animal models show that diet restriction (DR) decreases 5-HT metabolism in the brain and hypothalamus which is not necessarily associated with a decrease in the availability of essential amino acid tryptophan (TRP) the precursor of serotonin. To further investigate the mechanism involved in DR-induced decreases of 5-HT the present study uses 8-hydroxy-(2-di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT-1A agonist, as a probe to monitor the responsiveness of negative feedback control over 5-HT metabolism. Effects of DR and of 8-OHDPAT on TRP, 5-HT and 5-HIAA concentrations are determined in the hypothalamus, a region of the brain known to role in the regulation of appetite. Animals of DR group given access to food 2h daily for 6 days exhibited 21.6% decrease in the body weight compared to freely feeding (FF) controls. The levels of TRP in the plasma and of 5-HT in the hypothalamus decreased. No effect was found on the levels of TRP in the hypothalamus. 8-OH-DPAT-induced decreases of 5-HT and 5-HIAA were greater in DR than FF group. 8-OH-DPAT-induced hyperactivity was also greater in DR than FF group. The results show that DR-induced decreases of 5-HT are due to an increase in the responsiveness of negative feedback control over 5-HT and not due to smaller availability of TRP. DR-induced increase in activity and 8-OH-DPAT-induced greater hyperactivity in DR than FF group may also be due to exaggerated negative feedback control over 5-HT. It is suggested that drugs decreasing the responsiveness of negative feedback control over 5-HT may be of use for the treatment and prevention of AN in under weight patients on restricted diet.
authors: Department of Biochemistry, Neurochemistry and Biochemical Neuropharmacology Research Unit, University of Karachi, Karachi 75270, Pakistan. darakhshan_haleem@yahoo.com
authors: Darakhshan Jabeen
authors: DJ
authors: Haleem
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000818:Animals; D000856:Anorexia Nervosa / Q000209:etiology / Q000503:physiopathology*; D001923:Brain Chemistry / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D005260:Female; D005508:Food Deprivation; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007031:Hypothalamus / Q000737:chemistry / Q000187:drug effects; D011595:Psychomotor Agitation / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage
chemical_list: D017366:Serotonin Receptor Agonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin