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NEUROCHEMICAL AND NEUROPHARMACOLOGICAL STUDIES OF SEROTONERGIC REGULATION OF APPETITE

Haider, Saida (2001) NEUROCHEMICAL AND NEUROPHARMACOLOGICAL STUDIES OF SEROTONERGIC REGULATION OF APPETITE. PhD thesis, University of Karachi, Karachi.

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Abstract

5-Hydroxytryptamine (5-HT; serotonin) is important in the regulation of appetite and food intake. Pharmacological manipulations which increase 5-HT functions in the brain} decrease feeding in experimental animals. Conversely, drugs that decrease brain serotonin functions have been shown to elicit feeding. This relationship between brain 5-HT and appetite is not consistent with clinical studies. Suppression of appetite observed in anorexia nervosa was not associated with an increase in cerebrospinal fluid (CSF) levels of 5-hydroxy indole acetic acid (5-HIAA). On the other hand, underweight patients with clinical symptoms of anorexia nervosa exhibited smaller 5-HIAA levels in the CSF. Excessive food restriction /dieting and weight loss may contribute to the development of anorexia nervosa. Brain 5-HT metabolism is also increased after starvation. To investigate the role of serotonin in food restriction-induced- anorexia nervosa in the present study, effects of short and long term food restriction were monitored on brain and hypothalamic 5-HT metabolism, synthesis and functional responses in rats.. The animals were fed on restricted feeding (RF) schedule of one week or four week and killed in either starved (RF starved) or fed (RF-fed) condition to monitor 5-HT metabolism and synthesis. Functional responses to a hypophagic serotonin agonist metachlorophenyl piperazine (mCPP) were also monitored in freely feeding (FF) and RF group in both starved and fed condition. Important findings of the study are as follows: Food restriction of one week produced a 16% reduction in body weight of male rats. 5-HT levels decreased particularly in the hypothalamus. Tryptophan (TRP) levels in the plasma and brain were not affected. 5-HlAA levels increased only in the RF starved rats. . One week of food restriction decreased 5-HT synthesis in the hypothalamus of the rats. Synthesis of catecholamines was not altered. Oral administration of TRP for 5 weeks increased plasma TRP and brain TRP, 5-HT and 5-HlAA levels but food intakes of animals were not affected. Body weight increased significantly only in the 5th week. Food restriction of 4 weeks produced a reduction in body weight of 25.4% and 20.4% respectively in male and female rats. Plasma TRP levels decreased in RF starved male rats and RF starved and fed females. TRP levels in the hypothalami decreased in RF-fed male rats and RF-fed and RF-starved female rats. 5-HT levels in the hYpothalami decreased comparably in both RF starved and RF fed male and female rats. In the rest of the brain 5-HT levels decreased only in male rats in both fed and starved conditions. Brain TRP and 5-HlAA levels in both male and female rats were not affected. m-CPP a 5-HT-2C agonist injected at a submaxima dose of 5 mg/kg decreased both 2h and 4h food intake of FF male rats deprived of food for 24h but not of FF-non-food deprived male rats. In the RF group drug administration decreased 2h and 4h food intakes in both food deprived and non-deprived conditions. The decreases were greater in food deprived than non-deprived animals. Open arm exploratory activity in a plus maze and activity in an open field decreased following m-CPP injection. The decreases were comparable in food deprived and non-deprived rats of FF and RF groups.

Item Type:Thesis (PhD)
Uncontrolled Keywords:serotonergic regulation, appetite, 5-ht; serotonin, m-cpp, monoamine neurotransmitters, hypothalamus, trp ingestion, anorexia nervosa
Subjects:Physical Sciences (f) > Chemistry(f2)
ID Code:1255
Deposited By:Mr. Muhammad Asif
Deposited On:18 Jan 2007
Last Modified:04 Oct 2007 21:05

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