The utility of animal models to evaluate novel anti-obesity agents

British Journal of Pharmacology

Volumn 164, Issue 4, 2011, Pages 1248-1262

  Vickers, Steven P ^a   Jackson, Helen C ^a   Cheetham, Sharon C ^a  

^a RenaSci Ltd   (United Kingdom)

Author keywords

animal models; anti obesity drug; DIO; obesity; Qnexa

Indexed keywords

AMFEBUTAMONE PLUS NALTREXONE; AMINOREX; ANTIOBESITY AGENT; CANNABINOID 1 RECEPTOR ANTAGONIST; CE 178253; DAVALINTIDE; DEXFENFLURAMINE; DNA; E 6837; EXENDIN 4; FENFLURAMINE; KAOLIN; LEPTIN; LORCASERIN; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; METRELEPTIN; PHENTERMINE; PHENTERMINE PLUS TOPIRAMATE; PRAMLINTIDE; RIMONABANT; SEROTONIN 6 AGONIST; SEROTONIN AGONIST; SIBUTRAMINE; TETRAHYDROLIPSTATIN; TOPIRAMATE; UNCLASSIFIED DRUG;

ANXIETY; BODY FAT; CALORIC INTAKE; CARDIOVASCULAR DISEASE; CONDITIONING; DEPRESSION; DISEASE MODEL; DNA MODIFICATION; DRUG APPROVAL; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG MARKETING; DRUG POTENTIATION; DRUG RESEARCH; DRUG SAFETY; DRUG SCREENING; ENERGY EXPENDITURE; EUROPE; FEEDING BEHAVIOR; FOOD AND DRUG ADMINISTRATION; FOOD AVAILABILITY; FOOD AVERSION; FOOD INTAKE; HUMAN; LIPID DIET; MALAISE; METABOLIC RATE; MOUSE; NAUSEA; NONHUMAN; OBESITY; PHYSICAL ACTIVITY; PICA; POSTMARKETING SURVEILLANCE; PREDICTION; PREDICTIVE VALIDITY; PRIORITY JOURNAL; PSYCHOLOGICAL ASPECT; PULMONARY HYPERTENSION; RAT; REVIEW; RODENT; SATIETY; SIDE EFFECT; SPECIES DIFFERENCE; SUICIDAL IDEATION; THERMOGENESIS; TOXICITY TESTING; UNITED STATES; VALVULAR HEART DISEASE; WEIGHT REDUCTION;

ANIMALS; ANTI-OBESITY AGENTS; APPETITE DEPRESSANTS; DISEASE MODELS, ANIMAL; FEEDING BEHAVIOR; FEMALE; HUMANS; MALE; OBESITY; SATIETY RESPONSE; TIME FACTORS;

EID: 80052943665     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2011.01245.x     Document Type: Review

References (132)

1. Antin J, Gibbs J, Holt J, Young RC, Smith GP, (1975). Cholecystokinin elicits the complete behavioral sequence of satiety in rats. J Comp Physiol Psychol 89: 784-790.
2. Apfelbaum M, Vague P, Ziegler O, Hanotin C, Thomas F, Leutenegger E, (1999). Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine. Am J Med 106: 179-184. (Pubitemid 29115958)
3. Arévalo C, de Miguel R, Hernández-Tristán R, (2001). Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters. Pharmacol Biochem Behav 70: 123-131. (Pubitemid 32786974)
4. Asarian L, Geary N, (2006). Modulation of appetite by gonadal steroid hormones. Philos Trans R Soc Lond B Biol Sci 361: 1251-1263.
5. Ator NA, Griffiths RR, (2003). Principles of drug abuse liability assessment in laboratory animals. Drug Alcohol Depend 70 (Suppl.): S55-S72. (Pubitemid 36577515)
6. Bailey CJ, Flatt PR, (2003). Animal syndromes resembling type 2 diabetes. In:, Pickup JC, Williams G, (eds). Textbook of Diabetes, 3rd edn. Blackwell Publishing: Oxford, pp. 25.1-25.30.
7. Bell CG, Walley AJ, Froguel P, (2005). The genetics of human obesity. Nat Rev Genet 6: 221-234. (Pubitemid 40293032)
8. Benoit SC, Air EL, Wilmer K, Messerschmidt P, Hodge KM, Jones MB, et al,. (2003). Two novel paradigms for the simultaneous assessment of conditioned taste aversion and food intake effects of anorexic agents. Physiol Behav 79: 761-766. (Pubitemid 37087972)
9. Beyer CE, Dwyer JM, Piesla MJ, Platt BJ, Shen R, Rahman Z, et al,. (2010). Depression-like phenotype following chronic CB1 receptor antagonism. Neurobiol Dis 39: 148-155.
10. Blundell JE, Hill AJ, (1988). On the mechanism of action of dexfenfluramine: effect on alliesthesia and appetite motivation in lean and obese subjects. Clin Neuropharmacol 11 (Suppl. 1): S121-S134.
11. Bradbury MJ, Campbell U, Giracello D, Chapman D, King C, Tehrani L, et al,. (2005). Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice. J Pharmacol Exp Ther 313: 395-402. (Pubitemid 40411366)
12. Bray GA, (2001). Drug treatment of obesity. Rev Endocr Metab Disord 2: 403-418. (Pubitemid 33640589)
13. Bray GA, Hollander P, Klein S, Kushner R, Levy B, Fitchet M, et al,. (2003). A 6-month randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 11: 722-733. (Pubitemid 41151598)
14. Brenot F, Herve P, Petitpretz P, Parent F, Duroux P, Simonneau G, (1993). Primary pulmonary hypertension and fenfluramine use. Br Heart J 70: 537-541. (Pubitemid 24009966)
15. Buettner R, Parhofer KG, Woenckhaus M, Wrede CE, Kunz-Schughart LA, Schölmerich J, et al,. (2006). Defining high-fat-diet rat models: metabolic and molecular effects of different fat types. J Mol Endocrinol 36: 485-501. (Pubitemid 43904942)
16. Clapham JC, Arch JRS, (2007). Thermogenic and metabolic antiobesity drugs: rationale and opportunities. Diabetes Obes Metab 9: 259-275. (Pubitemid 46502043)
17. Clegg DJ, Benoit SC, Fisher ME, Barrera JG, Seeley RJ, Woods SC, (2003a). Sex hormones determine body fat distribution and sensitivity to adiposity signals. Appetite 40: 324.
18. Clegg DJ, Riedy CA, Smith KA, Benoit SC, Woods SC, (2003b). Differential sensitivity to central leptin and insulin in male and female rats. Diabetes 52: 682-687. (Pubitemid 36323575)
19. Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, et al,. (1998). A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392: 398-401. (Pubitemid 28168737)
20. Coleman DL, (1978). Diabetes and obesity: thrifty mutants? Nutr Rev 36: 129-132.
21. Colombo G, Agabio R, Diaz G, Lobina C, Reali R, Gessa GL, (1998). Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci 63: PL113-PL117.
22. Connoley IP, Liu YL, Frost I, Reckless IP, Heal DJ, Stock MJ, (1999). Thermogenic effects of sibutramine and its metabolites. Br J Pharmacol 126: 1487-1495. (Pubitemid 29142081)
23. Connolly HM, Crary JL, McGoon MD, Hensrud DD, Edwards BS, Edwards WD, et al,. (1997). Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 337: 581-588. (Pubitemid 27360757)
24. Correia MLG, Haynes WG, (2007). Lessons from leptin's molecular biology: potential therapeutic actions of recombinat leptin and leptin-related compounds. Mini Rev Med Chem 7: 31-38. (Pubitemid 46062371)
25. Cypess AM, Kahn CR, (2010). Brown fat as a therapy for obesity and diabetes. Curr Opin Endocrinol Diabetes Obes 17: 143-149.
26. Day C, Bailey CJ, (1998). Effect of the antiobesity agent sibutramine in obese-diabetic ob/ob mice. Int J Obes Relat Metab Disord 22: 619-623. (Pubitemid 28312770)
27. Després JP, Golay A, Sjöström L, (2005). Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 353: 2121-2134. (Pubitemid 41653104)
28. Dickinson K, North TJ, Anthony DM, Jones RB, Heal DJ, (1998). Evaluation of a simplified cafeteria model for the induction of insulin resistant obesity in rats. Int J Obes 22 (Suppl. 3): S179.
29. Elangbam CS, (2009). Review paper: current strategies in the development of anti-obesity drugs and their safety concerns. Vet Pathol 46: 10-24.
30. Ellero C, Han J, Bhavsar S, Cirincione BB, Deyoung MB, Gray AL, et al,. (2010). Prophylactic use of anti-emetic medications reduced nausea and vomiting associated with exenatide treatment: a retrospective analysis of an open-label, parallel-group, single-dose study in healthy subjects. Diabet Med 27: 1168-1173.
31. EMEA (2008). The European Medicines Agency recommends suspension of the marketing authorisation of Acomplia.
32. EMEA (2010). European Medicines Agency recommends suspension of marketing authorisation for sibutramine.
33. Farooqi IS, O'Rahilly S, (2008). Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 4: 569-577.
34. Farooqi IS, O'Rahilly S, (2009). Leptin: a pivotal regulator of human energy homeostasis. Am J Clin Nutr 89: 980S-984S.
35. Fisas A, Codony X, Romero G, Dordal A, Giraldo J, Mercé R, et al,. (2006). Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats. Br J Pharmacol 148: 973-983. (Pubitemid 44543615)
36. Gadde KM, Allison DB, (2009). Combination therapy for obesity and metabolic disease. Curr Opin Endocrinol Diabetes Obes 16: 353-358.
37. Greenway FL, Whitehouse MJ, Guttadauria M, Anderson JW, Atkinson RL, Fujioka K, et al,. (2009). Rational design of a combination medication for the treatment of obesity. Obesity 17: 30-39. (Pubitemid 50324544)
38. Griebel G, Stemmelin J, Scatton B, (2005). Effects of the canabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents. Biol Psychiatry 57: 261-267. (Pubitemid 40187370)
39. Hadcock JR, Carpino PA, Iredale PA, Dow RL, Gautreau D, Thiede L, et al,. (2010). Quantitative in vitro and in vivo pharmacological profile of CE-178253, a potent and selective cannabinoid type 1(CB1) receptor antagonist. BMC Pharmacol 10: 9.
40. Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM, (1997). Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci USA 94: 8878-8883. (Pubitemid 27335133)
41. Halford JC, Wanninayake SC, Blundell JE, (1998). Behavioural satiety sequence (BSS) for the diagnosis of drug action on food intake. Pharmacol Biochem Behav 61: 159-168. (Pubitemid 28458908)
42. Halford JCG, Boyland EJ, Blundell JE, Kirkham TC, Harrold JA, (2010). Pharmacological management of appetite expression in obesity. Nat Rev Endocrinol 6: 255-269.
43. Hansen DL, Toubro S, Stock MJ, Macdonald IA, Astrup A, (1998). Thermogenic effects of sibutramine in humans. Am J Clin Nutr 68: 1180-1186. (Pubitemid 28550946)
44. Hansen DL, Toubro S, Stock MJ, Macdonald IA, Astrup A, (1999). The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction. Int J Obes Relat Metab Disord 23: 1016-1024. (Pubitemid 29476203)
45. Hansen HH, Hansen G, Tang-Christensen M, Larsen PJ, Axel AM, Raben A, et al,. (2010). The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant. Eur J Pharmacol 636: 88-95.
46. Harrold JA, Widdowson PS, Clapham JC, Williams G, (2000). Individual severity of dietary obesity in unselected Wistar rats: relationship with hyperphagia. Am J Physiol Endocrinol Metab 279: E340-E347.
47. Hauptman J, Lucas C, Boldrin MN, Collins H, Segal KR, (2000). Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med 9: 160-167.
48. Heal DJ, Smith SL, Fisas A, Codony X, Buschmann H, (2008). Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol Ther 117: 207-231.
49. Heal DJ, Gosden J, Smith SL, (2009). Regulatory challenges for new drugs to treat obesity and comorbid metabolic disorders. Br J Clin Pharmacol 68: 861-874.
50. 6 Receptors, Part II. Academic Press: Oxford, pp. 73-109.
51. Hewitt KN, Lee MD, Dourish CT, Clifton PG, (2002). Serotonin 2C receptor agonists and the behavioural satiety sequence in mice. Pharmacol Biochem Behav 71: 691-700. (Pubitemid 34219219)
52. Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, et al,. (1999). Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282: 1568-1575. (Pubitemid 29504050)
53. Hirst WD, Abrahamsen B, Blaney FE, Calver AR, Aloj L, Price GW, et al,. (2003). Differences in the central nervous system distribution and pharmacology of the mouse 5-hydroxytryptamine-6 receptor compared with rat and human receptors investigated by radioligand binding, site-directed mutagenesis, and molecular modelling. Mol Pharmacol 64: 1295-1308. (Pubitemid 37532219)
54. Hogan S, Fleury A, Hadvary P, Lengsfeld H, Meier MK, Triscari J, et al,. (1987). Studies on the antiobesity activity of tetrahydrolipstatin, a potent and selective inhibitor of pancreatic lipase. Int J Obes 11 (Suppl. 3): 35-42. (Pubitemid 18012894)
55. Hunt T, Amit Z, (1987). Conditioned taste aversion induced by self-administered drugs: paradox revisited. Neurosci Biobehav Rev 11: 107-130. (Pubitemid 17042721)
56. Ingalls AM, Dickie MM, Snell GD, (1950). Obese, a new mutation in the house mouse. J Hered 41: 317-318.
57. Jackson HC, Needham AM, Hutchins LJ, Mazurkiewicz SE, Heal DJ, (1997). Comparison of the effects of sibutramine and other monoamine reuptake inhibitors on food intake in the rat. Br J Pharmacol 121: 1758-1762. (Pubitemid 27343407)
58. Jackson HC, Pleasance IM, Mitchell JM, Heal DJ, (2000). Observational analysis of the effects of sibutramine, phentermine and aminorex on food intake in rats. Obes Res 8 (Suppl. 1): 95S.
59. Jackson HC, Dickinson K, Jones RB, Schumacher C, Jensen C, (2004). Comparison of the effects of sibutramine and orlistat on body weight, food and water intake and body composition in dietary-induced obese rats. Neuroscience Program No 75.3 Neuroscience Meeting Planner, Society for Neuroscience: San Diego, CA. Online.
60. Jackson HC, Cheetham SC, Dickinson K, Jones RB, Heal DJ, Gregory P, et al,. (2005). Comparison of the effects of rimonabant and sibutramine in a rat model of dietary-induced obesity. Neuroscience Program No 532.13 Neuroscience Meeting Planner, Society for Neuroscience: Washington, DC. Online.
61. Jackson HC, Cheetham SC, Gregory PC, Antel J, (2007). Effect of chronic administration of topiramate and phentermine, alone and in combination, in an animal model of dietary-induced obesity. 629.15. Neuroscience Program No 629.15 Neuroscience Meeting Planner, Society for Neuroscience: San Diego, CA. Online.
62. James WP, Astrup A, Finer N, Hilsted J, Kopelman P, Rössner S, et al,. (2000). Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet 356: 2119-2125.
63. Jones RB, Dickinson K, Sands S, Skill MJ, Heal DJ, Kilpatrick IC, (2001). Effect of chronic administration of sibutramine on body composition analysis of lean and obese female rats. Obes Res 9: 118S.
64. Kennedy AJ, Ellacott KLJ, King VL, Hasty AH, (2010). Mouse models of the metabolic syndrome. Dis Model Mech 3: 156-166.
65. Kennett GA, Clifton PG, (2010). New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier? Pharmacol Biochem Behav 97: 63-83.
66. Kitchener SJ, Dourish CT, (1994). An examination of the behavioural specificity of hypophagia induced by 5-HT1B, 5-HT1C and 5-HT2 receptor agonists using the post-prandial satiety sequence in rats. Psychopharmacology (Berl) 113: 369-377. (Pubitemid 24150482)
67. Kotsis V, Stabouli S, Bouldin M, Low A, Toumanidis S, Zakopoulos N, (2005). Impact of obesity on 24-hour ambulatory blood pressure and hypertension. Hypertension 45: 602-607. (Pubitemid 40411267)
68. Kris-Etherton PM, Dietschy J, (1997). Design criteria for studies examining individual fatty acid effects on cardiovascular disease risk factors: human and animal studies. Am J Clin Nutr 65 (Suppl.): 1590S-1596S. (Pubitemid 27187953)
69. Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE, (1997). Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol 273: R725-R730.
70. Li S, Zhang HY, Hu CC, Lawrence F, Gallagher KE, Surapaneni A, et al,. (2008). Assessment of diet-induced obese rats as an obesity model by comparative functional genomics. Obesity 16: 811-818. (Pubitemid 351465637)
71. Lobley GE, Bremner DM, Holtrop G, Johnstone AM, Maloney C, (2007). Impact of high-protein diets with either moderate or low carbohydrate on weight loss, body composition, blood pressure and glucose tolerance in rats. Br J Nutr 97: 1099-1108. (Pubitemid 46925362)
72. Mack CM, Moore CX, Jodka CM, Bhavsar S, Wilson JK, Hoyt JA, et al,. (2006). Antiobesity action of peripheral exenatide (exendin-4) in rodents: effects on food intake, body weight, metabolic status and side-effect measures. Int J Obes 30: 1332-1340. (Pubitemid 44306514)
73. Mack CM, Soares CJ, Wilson JK, Athanacio JR, Turek VF, Trevaskis JL, et al,. (2010). Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int J Obes 34: 385-395.
74. Madsen AN, Hansen G, Paulsen SJ, Lykkegaard K, Tang-Christensen M, Hansen HS, et al,. (2010). Long-term characterization of the diet-induced obese and diet-resistant rat model: a polygenetic rat model mimicking the human obesity syndrome. J Endocrinol 206: 287-296.
75. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al,. (1995). Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1: 1155-1161.
76. Masek J, Fabry P, (1959). High-fat diet and the development of obesity in albino rats. Experientia 15: 444-445.
77. Matsumoto K, Iijima H, (2003). Sibutramine sensitivity assay revealed a unique phenotype of bombesin BB3 receptor-deficient mice. Eur J Pharmacol 473: 41-46. (Pubitemid 36857095)
78. Miesel A, Müller H, Thermann M, Heidbreder M, Dominiak P, Raasch W, (2010). Overfeeding-induced obesity in spontaneously hypertensive rats: an animal model of the human metabolic syndrome. Ann Nutr Metab 56: 127-142.
79. Mohapatra J, Sharma M, Singh S, Pandya G, Chatterjee A, Balaraman R, et al,. (2009). Involvement of adipokines in rimonabant-mediated insulin sensitivity in ob/ob mice. J Pharm Pharmacol 61: 1493-1498.
80. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al,. (1997). Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387: 903-908. (Pubitemid 27289591)
81. Mutch DM, Clément K, (2006). Unraveling the genetics of human obesity. PloS Genet 2: e188.
82. Naderali EK, Pickavance LC, Wilding JP, Williams G, (2001). Diet-induced endothelial dysfunction in the rat is independent of the degree of increase in total body weight. Clin Sci (Lond) 100: 635-641. (Pubitemid 32523316)
83. Navarro M, Hernández E, Muñoz RM, del Arco I, VillanÃa MA, Carrera MR, et al,. (1997). Acute administration of the CB1 cannabinoid receptor antagonist SR 141716A induces anxiety-like responses in the rat. Neuroreport 8: 491-496. (Pubitemid 27180108)
84. Neill JC, Cooper SJ, (1989). Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors. Psychopharmacology (Berl) 97: 213-218. (Pubitemid 19040164)
85. Parker LA, Limebeer CL, (2006). Conditioned gaping in rats: a selective measure of nausea. Auton Neurosci 129: 36-41. (Pubitemid 44470862)
86. Patel S, Hillard CJ, (2006). Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signalling. J Pharmacol Exp Ther 318: 304-311.
87. Pierroz DD, Ziotopoulou M, Ungsunan L, Moschos S, Flier JS, Mantzoros CS, (2002). Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity. Diabetes 51: 1337-1345. (Pubitemid 34826597)
88. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J, (2006). Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA 295: 761-775. (Pubitemid 43244304)
89. Poncelet M, Maruani J, Calassi R, Soubrié P, (2003). Overeating, alcohol and sucrose consumption decrease in CB1 receptor deleted mice. Neurosci Lett 343: 216-218. (Pubitemid 38365988)
90. Powell DR, (2006). Obesity drugs and their targets: correlation of mouse knockout phenotypes with drug effects in vivo. Obes Rev 7: 89-108.
91. Ravinet-Trillou C, Arnone M, Delgorge C, Gonalons N, Keane P, Maffrand JP, et al,. (2003). Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 284: R345-R353. (Pubitemid 36120150)
92. Ravussin E, Smith SR, Mitchell JA, Shringarpure R, Shan K, Maier H, et al,. (2009). Enhanced weight-loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity 17: 1736-1743.
93. Rodgers RJ, Holch P, Tallett AJ, (2010). Behavioural satiety sequence (BSS): separating wheat from chaff in the behavioural pharmacology of appetite. Pharmacol Biochem Behav 97: 3-14.
94. Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, et al,. (2008). Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 105: 7257-7262. (Pubitemid 351754465)
95. Saraà F, Pehlivan M, Celebi G, Saygili F, Yilmaz C, Kabalak T, (2006). Effects of sibutramine on thermogenesis in obese patients assessed via immersion calorimetry. Adv Ther 23: 1016-1029. (Pubitemid 46341059)
96. Seeley RJ, Blake K, Rushing PA, Benoit S, Eng J, Woods SC, et al,. (2000). The role of CNS glucagon-like peptide-1 (7-36) amide receptors in mediating the visceral illness effects of lithium chloride. Neurosci 20: 1616-1621. (Pubitemid 30220440)
97. Shearman LP, Camacho RE, Sloan Stribling D, Zhou D, Bednarek MA, Hreniuk DL, et al,. (2003). Chronic MCH-1 receptor modulation alters appetite, body weight and adiposity in rats. Eur J Pharmacol 475: 37-47. (Pubitemid 37088004)
98. Silva JE, (1995). Thyroid hormone control of thermogenesis and energy balance. Thyroid 5: 481-492. (Pubitemid 26036911)
99. Silvani A, Bastianini S, Berteotti C, Franzini C, Lenzi P, Lo Martire V, et al,. (2009). Sleep modulates hypertension in leptin-deficient obese mice. Hypertension 53: 251-255.
100. Skill MJ, Dickinson K, Jones RB, Heal DJ, (2000). Thermogenic effect of repeated sibutramine treatment in female Wistar rats. Int J Obes 24 (Suppl.): S135.
101. Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, et al,. (2008). Discovery and structure-activity relationship of (1R)-chloro-2,3,4,5- tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J Med Chem 51: 305-313.
102. Smith SR, Weissman NJ, Anderson CM, Sanchez M, Chuang E, Stubbe S, et al,. (2010). Multicenter, placebo-controlled trial of lorcaserin for weight management. Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. N Engl J Med 363: 245-256.
103. Stock MJ, (1975). An automatic, closed-circuit oxygen consumption apparatus for small animals. J Appl Physiol 39: 849-850.
104. Su W, Guo Z, Randall DC, Cassis L, Brown DR, Gong MC, (2008). Hypertension and disrupted blood pressure circadian rhythm in type 2 diabetic db/db mice. Am J Physiol Heart Circ Physiol 295: H1634-H1641.
105. Swinburn BA, Sacks G, Lo SK, Westerterp KR, Rush EC, Rosenbaum M, et al,. (2009). Estimating the changes in energy flux that characterize the rise in obesity prevalence. Am J Clin Nutr 89: 1723-1728.
106. Takeda N, Hasegawa S, Morita M, Matsunaga T, (1993). Pica in rats is analogous to emesis: an animal model in emesis research. Pharmacol Biochem Behav 45: 817-821.
107. Takeda N, Hasegawa S, Morita M, Horii A, Uno A, Yamatodani A, et al,. (1995a). Neuropharmacological mechanisms of emesis. I. Effects of antiemetic drugs on motion- and apomorphine-induced pica in rats. Methods Find Exp Clin Pharmacol 17: 589-596. (Pubitemid 26029813)
108. Takeda N, Hasegawa S, Morita M, Horii A, Uno A, Yamatodani A, et al,. (1995b). Neuropharmacological mechanisms of emesis. II. Effects of antiemetic drugs on cisplatin-induced pica in rats. Methods Find Exp Clin Pharmacol 17: 647-652. (Pubitemid 26054642)
109. Tallett AJ, Blundell JE, Rodgers RJ, (2007). Grooming, scratching and feeding: role of response competition in acute anorectic response to rimonabant in male rats. Psychopharmacology 195: 27-39. (Pubitemid 47568626)
110. Tallett AJ, Blundell JE, Rodgers RJ, (2009). Sibutramine-induced anorexia: potent, dose-dependent and behaviourally-selective profile in male rats. Behav Brain Res 198: 359-365.
111. Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, et al,. (1995). Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature 374: 542-546.
112. Thiele TE, Van Dijk G, Campfield LA, Smith FJ, Burn P, Woods SC, et al,. (1997). Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats. Am J Physiol 272 (Pt 2): R726-R730.
113. 1A receptor agonists and norepinephrine reuptake inhibitors that reduce food intake and body weight in animal models of obesity. Progran No 62.4 Neuroscience Meeting Planner. Society for Neuroscience: Atlanta, GA. Online.
114. Thomsen WJ, Grottick AJ, Menzaghi F, Reyes-Saldana H, Espitia S, Yuskin D, et al,. (2008). Lorcaserin, a novel selective human 5-hydroxytryptamine2C agonist: in vitro and in vivo pharmacological characterization. J Pharmacol Exp Ther 325: 577-587. (Pubitemid 351574813)
115. Thornton-Jones ZD, Kennett GA, Benwell KR, Revell DF, Misra A, Sellwood DM, et al,. (2006). The cannabinoid CB1 receptor inverse agonist, rimonabant, modifies body weight and adiponectin function in diet-induced obese rats as a consequence of reduced food intake. Pharmacol Biochem Behav 84: 353-359. (Pubitemid 44137303)
116. Trevaskis JL, Coffey T, Cole R, Lei C, Wittmer C, Walsh B, et al,. (2008). Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology 149: 5679-5687.
117. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rössner S, (2005). Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365: 1389-1397. (Pubitemid 40523733)
118. Verty AN, McGregor IS, Mallet PE, (2004). Consumption of high carbohydrate, high fat, and normal chow is equally suppressed by a cannabinoid receptor antagonist in non-deprived rats. Neurosci Lett 354: 217-220. (Pubitemid 38045348)
119. Vickers SP, Kennett GA, (2005). Cannabinoids and the regulation of ingestive behaviour. Curr Drug Targets 6: 215-223. (Pubitemid 40394316)
120. Vickers SP, Clifton PG, Dourish CT, (1996). Behavioural evidence that d-fenfluramine-induced anorexia in the rat is not mediated by the 5-HT1A receptor subtype. Psychopharmacology (Berl) 125: 168-175.
121. Vickers SP, Clifton PG, Dourish CT, Tecott LH, (1999). Reduced satiating effect of d-fenfluramine in serotonin 5-HT(2C) receptor mutant mice. Psychopharmacology (Berl) 143: 309-314. (Pubitemid 29204986)
122. Vickers SP, Benwell KR, Porter RH, Bickerdike MJ, Kennett GA, Dourish CT, (2000). Comparative effects of continuous infusion of mCPP, Ro 60-0175 and d-fenfluramine on food intake, water intake, body weight and locomotor activity in rats. Br J Pharmacol 130: 1305-1314. (Pubitemid 30488594)
123. Vickers SP, Dourish CT, Kennett GA, (2001). Evidence that hypophagia induced by d-fenfluramine and d-norfenfluramine in the rat is mediated by 5-HT2C receptors. Neuropharmacology 41: 200-209. (Pubitemid 32728091)
124. Vickers SP, Easton N, Webster LJ, Wyatt A, Bickerdike MJ, Dourish CT, et al,. (2003a). Oral administration of the 5-HT2C receptor agonist, mCPP, reduces body weight gain in rats over 28 days as a result of maintained hypophagia. Psychopharmacology (Berl) 167: 274-280. (Pubitemid 36712974)
125. Vickers SP, Webster LJ, Wyatt A, Dourish CT, Kennett GA, (2003b). Preferential effects of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight gain of obese (fa/fa) compared to lean Zucker rats. Psychopharmacology (Berl) 167: 103-111. (Pubitemid 36535298)
126. Wajchenberg BL, (2000). Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocrinol Rev 21: 697-738. (Pubitemid 32113289)
127. Walsh KM, Leen E, Lean ME, (1999). The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females. Int J Obes Relat Metab Disord 23: 1009-1015. (Pubitemid 29476202)
128. Witkin JM, Tzavara ET, Nomikos GG, (2005). A role for cannabinoid CB1 receptors in mood and anxiety disorders. Behav Pharmacol 16: 315-331. (Pubitemid 41404804)
129. World Health Organisation (2011). Obesity and overweight: factsheet No 311.
130. Yamamoto K, Matsunaga S, Matsui M, Takeda N, Yamatodani A, (2002). Pica in mice as a new model for the study of emesis. Methods Find Exp Clin Pharmacol 24: 135-138. (Pubitemid 34534589)
131. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM, (1994). Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425-432. (Pubitemid 24365442)
132. Zucker LM, Zucker TF, (1961). Fatty. A new mutation in the rat. J Hered 52: 275-278.