I= NEUROCHEMICAL AND NEUROPHARMACOLOGICAL STUDIES OF SEROTONERGIC REGULATION OF APPETITE
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Title of Thesis
NEUROCHEMICAL AND NEUROPHARMACOLOGICAL STUDIES OF SEROTONERGIC REGULATION OF APPETITE

Author(s)
Saida Haider
Institute/University/Department Details
Department of Biochemistry/ University of Karachi
Session
2001
Subject
Number of Pages
256
Keywords (Extracted from title, table of contents and abstract of thesis)
serotonergic regulation, appetite, 5-ht; serotonin, m-cpp, monoamine neurotransmitters, hypothalamus, trp ingestion, anorexia nervosa

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.

Download Full Thesis
2539.05 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
156.28 KB
2 1 General Introduction 1
530.34 KB
  1.1 Appetite regulation 1
  1.2 Monoamine neurotransmitters 1
  1.3 Importance of hypothalamus in the regulation of feeding behavior 4
  1.4 Serotonin 5
  1.5 Factors affecting 5-HT synthesis 12
3 2 Materials and Methods 49
438.08 KB
  2.1 Animals and treatment 49
  2.2 Chemicals and drugs 49
  2.3 Food restriction procedure 51
  2.4 Behavioral methods 51
  2.5 Brain dissection technique 53
4 3 Effects of 5 day food restriction on brain regional serotonin metabolism in male rats 83
161.64 KB
  3.1 Experimental protocol 84
  3.2 Statistical analysis 85
  3.3 Results 85
  3.4 Discussion 96
5 4 Effects of 5 Day Food Restriction on 5-HT Synthesis in the Hypothalamus and Rest of the Brain of Starved and Fed Male Rats 100
89.75 KB
  4.1 Experimental Protocol 102
  4.2 Statistical analysis 102
  4.3 Results 102
  4.4 Discussion 105
6 5 Effects of 5 Weeks TRP Ingestion on Brain 5-HT Metabolism in Young Male Rats 109
99.06 KB
  5.1 Experimental protocol 110
  5.2 Statistical analysis 110
  5.3 Results 110
  5.4 Discussion 113
7 6 Effects of 4 Weeks of Food Restriction on Brain 5-HT Metabolism in Starved and Fed Male and Female Rats 121
260.33 KB
  6.1 Experimental Protocol 122
  6.2 Statistical analysis 124
  6.3 Results 124
  6.4 Discussion 134
8 7 Behavioral and Neurochemical Responses to m-CPP in FF and RF Fed and Starved Male Rats 141
211.11 KB
  7.1 Experimental Protocol 142
  7.2 Statistical analysis 143
  7.3 Results 143
  7.4 Discussion 160
9 8 Behavioral and Neurochemical Responses to m-CPP in FF and RF Fed and Starved Female Rats 164
193.98 KB
  8.1 Experimental protocol 165
  8.2 Statistical analysis 165
  8.3 Results 166
  8.4 Discussion 182
10 9 Conclusion 186
730.48 KB
  9.1 Role of precursor availability on 5-HT metabolism 187
  9.2 5-HT concentration and functional responses to 5-HT 189
  9.3 Sex differences of food restriction-induced 5-HT functions in the epidemiology of anorexia nervosa 190
  9.4 Implications 19.3
  9.5 Future Prospects 195
  9.6 References 197
  9.7 Publications from thesis 257