Psychopharmacology

, Volume 100, Issue 3, pp 426–432 | Cite as

Effects of nalmefene on feeding in humans

Dissociation of hunger and palatability
  • M. R. Yeomans
  • P. Wright
  • H. A. Macleod
  • J. A. J. H. Critchley
Original Investigations

Abstract

Effects of nalmefene on eating were investigated in two groups of ten male volunteers, in a double-blind placebo-controlled study. The nalmefene treated group ate 22% less, both in terms of absolute weight and caloric intake, of a standardised buffet-meal than did the placebo group. No differences in subjective ratings of hunger or satiety were found between the groups, suggesting that the reduced feeding was not a consequence of any change in motivation to eat. When analysed by nutrient content, nalmefene was found to reduce fat and protein, but not carbohydrate, intakes. Analyses of intakes of individual foods showed a differential effect of nalmefene on foods rated as highly palatable. Thus the apparent nutrient specificity of nalmefene appeared to be an indirect consequence of its effect on palatability. Nalmefene also caused slight increases in self-rated alertness, and decreases in ratings of tiredness and elation, although it was thought unlikely that these accounted for observed changes in eating behaviour. No other side-effects were detected, and performance on a choice reaction time task was unaffected. These results add weight to suggestions that endogenous opioids are involved in reward-related aspects of feeding associated with food palatability.

Key words

Feeding Humans Opioids Nalmefene Palatability 

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References

  1. Apfelbaum M, Mandenoff A (1981) Naltrexone suppresses hyperphagia induced in the rat by a highly palatable diet. Pharmacol Biochem Behav 15:89–91Google Scholar
  2. Atkinson RL (1982) Naloxone decreases food intake in obese humans. J Clin Endocrinol Metab 55:196–198Google Scholar
  3. Atkinson RL, Berke LK, Drake CR, Bibbs ML, Williams FL, Kaiser DL (1985) Effects of long-term therapy with naltrexone on body weight in obesity. Clin Pharmacol Ther 38:419–422Google Scholar
  4. Billington CJ, Morley JE, Levine AS, Wright F, Seal US (1985) Naloxone suppression of feeding in tigers. Physiol Behav 34:641–643Google Scholar
  5. Bozarth M (1988) Opioids and reinforcement. In: Rodgers RJ, Cooper SJ (eds) Endorphins, opiates and behavioural processes. Wiley, ChichesterGoogle Scholar
  6. Brands B, Thornhill JA, Hirst M, Gowdey CW (1979) Suppression of food intake and body weight gain by naloxone in rats. Life Sci 24:1773–1778Google Scholar
  7. Brown DR, Holtzman SG (1979) Suppression of deprivation-induced food and water intake in rats and mice by naloxone. Pharmacol Biochem Behav 11:567–573Google Scholar
  8. Carey MP, Ross JA, Enns MP (1981) Naloxone suppresses feeding and drinking but not wheel running in rats. Pharmacol Biochem Behav 14:569–571Google Scholar
  9. Chaves MLF, Bizzi JWJ, Palmini AL, Izquierdo I (1988) Naltrexone blocks the enhancing effect of novel experiences on performance in memory tests in humans. Neuropsychologia 26:491–494Google Scholar
  10. Cohen MR, Cohen RM, Pickar D, Weingartner H, Murphy DL (1983) High-dose naloxone infusion in normals. Arch Gen Psychiatry 40:613–619Google Scholar
  11. Cohen MR, Cohen RM, Pickar D, Murphy DL (1985) Naloxone reduces food intake in humans. Psychosom Med 47:132–138Google Scholar
  12. Cooper SJ, Turkish S (1981) Food and water intake in the non-deprived pigeon after morphine or naloxone administration. Neuropharmacology 20:1053–1058Google Scholar
  13. Cooper SJ, Barber DJ, Barbour-McMullen J (1985) Selective attenuation of sweetened milk consumption by opiate receptor antagonists in male and female rats of the Roman strains. Neuropeptides 5:349–352Google Scholar
  14. Cooper SJ, Jackson A, Kirkham TC, Turkish S (1988) Endorphins, opiates and food intake. In: Rodgers RJ, Cooper SJ (eds) Endorphins, opiates and behavioural processes. Wiley, Chichester, pp 143–186Google Scholar
  15. Deviche P, Wohland A (1984) Opiate antagonists stereoselectively attenuate the consumption of food but not of water by pigeons. Pharmacol Biochem Behav 21:507–512Google Scholar
  16. Dixon R, Gentile J, Hsu HB, Hsiao J, Howes J, Garg D, Weidler D (1987) Nalmefene: safety and kinetics after single and multiple oral doses of a new opioid antagonist. Clin Pharmacol 27:233–239Google Scholar
  17. Drewnowski A, Gosnell B, Krahn DD, Canum K (1989) Sensory preferences for sugar and fat: evidence for opioid involvement. Appetite 12; 206Google Scholar
  18. Fantino M, Hisotte J, Apfelbaum M (1988) An opioid antagonist, naltrexone, reduces preference for sucrose in humans. Am J Physiol 251:R91-R96Google Scholar
  19. Gai TJ, DiFazzio CA (1986) Prolonged antagonism of opioid action with intravenous nalmefene in man. Anesthesiology 64:175–180Google Scholar
  20. Grandison L, Guidotti A (1977) Stimulation of food intake by muscimol and beta endorphin. Neuropharmacology 16:533–536Google Scholar
  21. Holtzman SG (1979) Suppression of appetitive behaviour in the rat by naloxone: lack of prior morphine dependence. Life Sci 24:219–226Google Scholar
  22. Kavaliers M, Hirst M, Teskey GC (1985) Opioid systems and feeding in the slug,Limax maximus: similarities to and implications for mammalian feeding. Brain Res Bull 14:681–685Google Scholar
  23. Kirkham TC, Cooper SJ (1988) Attenuation of sham feeding by naloxone is stereo-specific: evidence for opioid mediation of orosensory reward. Physiol Behav 43; 845–847Google Scholar
  24. Le Magnen J, Marfaing-Jallat P, Miceli D, Devos M (1980) Pain modulating and reward systems: a single brain mechanism? Pharmacol Biochem Behav 12:729–733Google Scholar
  25. Lynch WC, Libby L (1983) Naloxone suppresses intake of highly preferred saccharin solutions in food-deprived and sated rats. Life Sci 33:1909–1914Google Scholar
  26. Malcolm R, O'Neill PM, Sexauer JD, Riddle FE, Currey HS, Counts C (1985) A controlled trial of naltrexone in obese humans. Int J Obes 9:347–353Google Scholar
  27. McCarthy G, Donchin E (1981) A metric for thought: a comparison of P300 latency and reaction time. Science 211:77–80Google Scholar
  28. McLaughlin CL, Baille CA (1983) Nalmefene decreases meal size, food and water intake and weight gain in Zucker rats. Pharmacol Biochem Behav 19:235–240Google Scholar
  29. Mandenoff A, Fumeron F, Apfelbaum M, Margules DL (1982) Endogenous opiates and energy balance. Science 215:1536–1538Google Scholar
  30. Michel ME, Bolgan G, Weisman B-A (1984) Binding of a new opiate antagonist, nalmefene, to rat brain membranes. Pharmacologist 26:101Google Scholar
  31. Mitchell JE, Morley JE, Levine AS, Hatsukami D, Gannon M, Pfohl D (1987) High-dose naltrexone therapy and dietary counseling for obesity. Biol Psychiatry 22:35–42Google Scholar
  32. Morley JE, Levine AS (1980) Stress induced eating is mediated through endogenous opiates. Science 209:1259–1261Google Scholar
  33. Morley JE, Levine AS (1983) Involvement of dynorphin and the kappa opioid receptor in feeding. Peptides 4:797–800Google Scholar
  34. O'Brien CP, Stunkard AJ, Ternes JW (1982) Absence of naloxone sensitivity in obese humans. Psychosom Med 44:215–218Google Scholar
  35. Paul AA, Southgate DAT (1978) McCance and Widdowson's the composition of foods, 4th edn. HMSO, LondonGoogle Scholar
  36. Peck RE (1958) The S.H.P. test; an aid to the detection and measurement of depression. Arch Gen Psychiatry 1:35–40Google Scholar
  37. Penicaud L, Thompson DA (1984) Effects of systemic or intracerebroventricular naloxone injection on basal and 2-deoxy-d-glucose-induced ingestive behaviour. Life Sci 35:2297–2302Google Scholar
  38. Polivy J (1976) Perception of calories and regulation of intake in restrained and unrestrained subjects. Addict Behav 1:237–243Google Scholar
  39. Reid LD (1985) Endogenous opioid peptides and regulation of drinking and feeding. Am J Clin Nutr 42:1099–1132Google Scholar
  40. Sanger DJ, McCarthy PS (1980) Differential effects of morphine on food and water intake in food deprived and freely-feeding rats. Psychopharmacology 72:103–106Google Scholar
  41. Schwartz JR, Pomegrantz JR, Egeth HE (1977) State and process limitations in information processing: an additive factors analysis. J Exp Psychol Hum Percept Perform 3:402–410Google Scholar
  42. Sewell RDE, Jawarhadal K (1980) Antagonism of 2-deoxy-d-glucose-induced hyperphagia by naloxone: possible involvement of endorphins. J Pharm Pharmacol 32:148–149Google Scholar
  43. Spiegel TA, Stunkard AJ, Shrager EE, O'Brien CP, Morrison MF, Stellar E (1987) Effect of naltrexone on food intake, hunger, and satiety in obese men. Physiol Behav 40:135–141Google Scholar
  44. Siviy SM, Reid LD (1983) Endorphinergic modulation of acceptability of pulative reinforcers. Appetite 4:249–257Google Scholar
  45. Trenchard E, Silverstone T (1982) Naloxone reduces the food intake of normal human volunteers. Appetite 4:43–50Google Scholar
  46. Wolkowitz OM, Doran AR, Cohen MR, Cohen RM, Wise TN, Pickar D (1985) Effect of naloxone on food consumption in obesity. N Engl J Med 313:327Google Scholar
  47. Wolkowitz OM, Doran AR, Cohen MR, Cohen RM, Wise TN, Pickar D (1988) Single-dose naloxone acutely reduces eating in obese humans: behavioral and biochemical effects. Biol Psychiatry 24:483–487Google Scholar
  48. Yeomans MR (1987) Control of drinking in domestic fowls. Unpublished PhD thesis, University of EdinburghGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • M. R. Yeomans
    • 1
  • P. Wright
    • 1
  • H. A. Macleod
    • 1
  • J. A. J. H. Critchley
    • 2
  1. 1.Department of PsychologyUniversity of EdinburghEdinburghUK
  2. 2.Department of Clinical PharmacologyRoyal InfirmaryEdinburghUK

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