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Feeding, drug abuse, and the sensitization of reward by metabolic need

  • Reward/Drug Abuse Mechanisms
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Abstract

The incentive-motivating effects of external stimuli are dependent, in part, upon the internal need state of the organism. The increased rewarding efficacy of food as a function of energy deficit, for example, has obvious adaptive value. The enhancement of food reward extends, however, to drugs of abuse and electrical brain stimulation, probably due to a shared neural substrate. Research reviewed in this paper uses lateral hypothalamic electrical stimulation to probe the sensitivity of the brain reward system and investigate mechanisms through which metabolic need, induced by chronic food restriction and streptozotocin-induced diabetes, sensitizes this system. Results indicate that sensitivity to rewarding brain stimulation varies inversely with declining body weight. The effect is not mimicked by pharmacological glucoprivation or lipoprivation in ad libitum fed animals; sensitization appears to depend on persistent metabolic need or adipose depletion. While the literature suggests elevated plasma corticosterone as a peripheral trigger of reward sensitization, sensitization was not reversed by meal-induced or pharmacological suppression of plasma corticosterone. Centrally, reward sensitization is mediated by opioid receptors, since the effect is reversed by intracerebroventricular (i.c.v.) infusion of naltrexone, TCTAP (μ antagonist) and nor-binaltorphimine (κ antagonist). The fact that these same treatments, as well as i.c.v. infusion of dynorphin A antiserum, block the feeding response to lateral hypothalamic stimulation suggests that feeding and reward sensitization are mediated by a common opioid mechanism. Using in vitro autoradiography, radioimmunoassays and a solution hybridization mRNA assay, brain regional μ and κ opioid receptor binding, levels of prodynorphin-derived peptides, and prodynorphin mRNA, respectively, were measured in food-restricted and diabetic rats. Changes that could plausibly be involved in reward sensitization are discussed, with emphasis on the increased dynorphin A1–8 and prodynorphin mRNA levels in lateral hypothalamic neurons that innervate the pontine parabrachial nucleus, where μ binding decreased and κ binding increased. Finally, the possible linkage between metabolic need and activation of a brain opioid mechanism is discussed, as is evidence supporting the relevance of these findings to drug abuse.

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References

  1. DiChiara, G., and North, R. A. 1992. Neurobiology of opiate abuse. Trends Pharmacol. Sci. 13:185–192.

    Article  CAS  Google Scholar 

  2. Wise, R. A., 1982. Common neural basis for brain stimulation reward, drug reward, and food reward. Pages 445–454,in Hoebel, B. G. and Novin, D. (eds.), The Neural Basis of Feeding and Reward, Haer Institute, Brunswick, Maine.

    Google Scholar 

  3. Gosnell, B. A., Lane, K. E., Bell, S. M., and Krahn, D. D., 1995. Intravenous morphine self-administration by rats with low vs high saccharin preferences. Psychopharmacol. 117:248–252.

    Article  CAS  Google Scholar 

  4. Sills, T. L., and Vaccarino, F. J., 1994. Individual differences in sugar intake predict the locomotor response to acute and repeated amphetamine administration. Psychopharmacol. 116:1–8.

    Article  CAS  Google Scholar 

  5. Carroll, M. E., and Meisch, R. A., 1984. Increased drug-reinforced behavior due to food deprivation. Advances in Behav. Pharmacol. 4:47–88.

    CAS  Google Scholar 

  6. Franklin, J. C., Schiele, B. C., Brozek, J., and Keys, A., 1948. Observations on human behavior in experimental semistarvation and rehabilitation. J. Clin. Psychol. 4:28–45.

    Article  PubMed  CAS  Google Scholar 

  7. Holderness, C. C., Brooks-Gunn, J., and Warren, M. P., 1993. Co-morbidity of eating disorders and substance abuse: Review of the literature. Int. J. Eating Disorders 16:1–34.

    Article  Google Scholar 

  8. Koob, G. F., 1992. Drugs of abuse: anatomy, pharmacology and function of reward pathways, Trends Pharmacol. Sci. 13:177–184.

    Article  PubMed  CAS  Google Scholar 

  9. Kornetsky, C., and Esposito, R. U., 1979. Euphorigenic drugs: effects on the reward pathways of the brain. Fed. Proc. 38:2473–2476.

    PubMed  CAS  Google Scholar 

  10. Wise, R. A., and Hoffman, D. C., 1992. Localization of drug reward mechanisms by intracranial injections. Synapse 10:247–263.

    Article  PubMed  CAS  Google Scholar 

  11. Markou, A., and Koob, G. F., 1991. Postcocaine anhedonia. An animal model of cocaine withdrawal. Neuropsychopharmacol. 4: 17–26.

    CAS  Google Scholar 

  12. Schulteis, G., Carrera, R., Markou, A., Gold, L. H., and Koob, G. F., 1993. Motivational consequences of naloxone-precipitated opiate withdrawal: a dose-response analysis. Neurosci. Abstr. 19: 1247.

    Google Scholar 

  13. Conover, K. L., and Shizgal, P., 1994. Competition and summation between rewarding effects of sucrose and lateral hypothalamic stimulation in the rat. Behav. Neurosci. 108:537–548.

    Article  PubMed  CAS  Google Scholar 

  14. Hernandez, L., and Hoebel, B. G., 1989. Food intake and lateral hypothalamic self-stimulation covary after medial hypothalamic lesions or ventral midbrain 6-hydroxydopamine injections that cause obesity. Behav. Neurosci. 103:412–422.

    Article  PubMed  CAS  Google Scholar 

  15. Jenck, F., Gratton, A., and Wise, R. A., 1987. Opioid receptor subtypes associated with ventral tegmental facilitation of lateral hypothalamic brain stimulation reward, Brain Res. 423:34–38.

    Article  PubMed  CAS  Google Scholar 

  16. West, T. E. G., and Wise, R. A., 1989. Nucleus accumbens injections of mu and delta but not kappa opioids facilitates hypothalamic brain stimulation reward. Neurosci. Abstr, 15:342.

    Google Scholar 

  17. Colle, L. M., and Wise, R. A., 1988. Effects of nucleus accumbens amphetamine on lateral hypothalamic brain stimulation reward. Brain Res. 459:361–368.

    Article  PubMed  CAS  Google Scholar 

  18. Bozarth, M. A., and Wise, R. A., 1981. Intracranial self-administration of morphine into the ventral tegmental area of rats. Life Sci. 28:551–555.

    Article  PubMed  CAS  Google Scholar 

  19. Goeders, N. E., Lane, J. D., and Smith, J. E., 1984. Self-administration of methionine enkephalin into the nucleus accumbens. Pharmacol. Biochem. Behav. 20:451–455.

    Article  PubMed  CAS  Google Scholar 

  20. Hoebel, B. G., Monaco, A. P., Hernandez, L., Aulisi, E. F., Stanley, B. G., and Lenard, L., 1983. Self-injection of amphetamine directly into the brain. Psychopharmacol. 81:158–163.

    Article  CAS  Google Scholar 

  21. Carr, G. D., and White, N. M., 1983. Conditioned place preference from intra-accumbens but not intra-caudate amphetamine injections. Life Sci. 33:2551–2557.

    Article  PubMed  CAS  Google Scholar 

  22. Phillips, A. G., and LePiane, F. G., 1980. Reinforcing effects of morphine microinjection into the ventral tegmental area. Pharmacol. Biochem. Behav. 12:965–968.

    Article  PubMed  CAS  Google Scholar 

  23. Evans, K. R., and Vaccarino, F. J., 1986. Intra-nucleus accumbens amphetamine: Dose-dependent effects on food intake. Pharmacol. Biochem. Behav. 25:1149–1151.

    Article  PubMed  CAS  Google Scholar 

  24. Mucha, R. F., and Iversen, S. D., 1986. Increased food intake after opioid microinjections into the nucleus accumbens and ventral tegmental area of rat. Brain Res. 397:214–224.

    Article  PubMed  CAS  Google Scholar 

  25. Bindra, D., 1978. How adaptive behavior is produced: A perceptual motivational alternative to response reinforcement. Behav. Brain Sci. 1:41–91.

    Article  Google Scholar 

  26. Berridge, K. C., 1991. Modulation of taste affect by hunger, caloric satiety, and sensory-specific satiety in the rat. Appetite 16: 103–120.

    Article  PubMed  CAS  Google Scholar 

  27. Cabanac, M., 1971. Physiological role of pleasure. Science 173: 1103–1107.

    Article  PubMed  CAS  Google Scholar 

  28. Blundell, J. E., and Herberg, L. J., 1968. Relative effects of nutritional deficit and deprivation period on rate of electrical self-stimulation of the lateral hypothalamus. Nature 219:627–628.

    Article  PubMed  CAS  Google Scholar 

  29. Carr, K. D., and Wolinsky, T. D., 1993. Chronic food restriction and weight loss produce opioid facilitation of perifornical hypothalamic self-stimulation. Brain Res. 607:11–148.

    Article  Google Scholar 

  30. Abrahamsen, G. C., Berman, Y., and Carr, K. D., 1995. Curve-shift analysis of self-stimulation in food-restricted rats: relationship between daily meal, plasma corticosterone and reward sensitization. Brain Res. 695:186–194.

    Article  PubMed  CAS  Google Scholar 

  31. Carlezon, W. A., and Wise, R. A., 1993. Morphine-induced potentiation of brain stimulation reward is enhanced by MK-801. Brain Res. 620:339–342.

    Article  PubMed  Google Scholar 

  32. Ranaldi, R., and Beninger, R. J., 1994. The effects of systemic and intracerebral injections of D1 and D2 agonists on brain stimulation reward. Brain Res. 651:283–292.

    Article  PubMed  CAS  Google Scholar 

  33. Jones, R. G., and Booth, D. A., 1975. Dose-response for 2-deoxy-D-glucose induced feeding and the involvement of peripheral factors. Physiol. Behav. 15:85–90.

    Article  PubMed  CAS  Google Scholar 

  34. Kanarek, R. B., Marks-Kaufman, R., Ruthazer, R., and Gualtieri, L., 1983. Increased carbohydrate consumption by rats as a function of 2-deoxy-D-glucose administration. Pharmacol. Biochem. Behav. 18:47–50.

    Article  PubMed  CAS  Google Scholar 

  35. Benoit, S. C., and Davidson, T. L., 1996. Interoceptive sensory signals produced by 24-hr food deprivation, pharmacological glucoprivation, and lipoprivation. Behav. Neurosci. 110:168–180.

    Article  PubMed  CAS  Google Scholar 

  36. Friedman, M. I., Tordoff, M. G., and Ramirez, I., 1986. Integrated metabolic control of food intake. Brain Res. Bull. 17:855–859.

    Article  PubMed  CAS  Google Scholar 

  37. Even, P., Coulaud, H., and Nicolaidis, S., 1988. Integrated metabolic control of food intake after 2-deoxy-Dglucose and nicotinic acid injection. Am. J. Physiol. 255:R82-R89.

    PubMed  CAS  Google Scholar 

  38. Frutiger, S. A., and Drinkwine, P., 1992. Effect of glucoprivation on self-stimulation rate-frequency functions. Physiol. Behav. 52: 313–319.

    Article  PubMed  CAS  Google Scholar 

  39. Gey, K., and Carlson, L. A. (eds.), 1971. Metabolic Effects of Nicotinic Acid and its Derivatives, Bern: Hans Huber.

    Google Scholar 

  40. Carr, K. D., 1994. Streptozotocin-induced diabetes produces a naltrexone-reversible lowering of threshold for lateral hypothalamic self-stimulation. Brain Res. 664:211–214.

    Article  PubMed  CAS  Google Scholar 

  41. Dallman, M. F., Strack, A. M., Akana, S. F., Bradbury, M. J., Hanson, E. S., Scribner, K. A., and Smith, M., 1993. Peast and famine: Critical role of glucocorticoids with insulin in daily energy flow. Front. Neuroendocrinol. 14:303–347.

    Article  PubMed  CAS  Google Scholar 

  42. Honma, K.-I., Honma, S., and Hiroshige, T., 1983. Critical role of food amount for prefeeding corticosterone peak in rats. Am. J. Physiol. 245:R339-R344.

    PubMed  CAS  Google Scholar 

  43. Joels, M., and de Kloet, E. R., 1992. Control of neuronal excitability by corticosteroid hormones. Trends Neurosci. 15:25–30.

    Article  PubMed  CAS  Google Scholar 

  44. Deroche, V., Piazza, P. V., Casolini, P., LeMoal, M., and Simon, H., 1993. Sensitization to the psychomotor effects of amphetamine and morphine induced by food restriction depends on corticosterone secretion. Brain Res. 611:352–356.

    Article  PubMed  CAS  Google Scholar 

  45. Deroche, V., Piazza, P. V., Casolini, P., Maccari, S., Le Moal, M., and Simon, H., 1992. Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion. Brain Res. 598:343–348.

    Article  PubMed  CAS  Google Scholar 

  46. Piazza, P. V., Maccari, S., Deminiere, J.-M., Le Moal, M., Mormede, P., and Simon, H., 1991. Corticosterone levels determine individual vulnerability to amphetamine self-administration. Proc. Natl. Acad. Sci. 88:2088–2092.

    Article  PubMed  CAS  Google Scholar 

  47. Rouge-Pont, F., Marinelli, M., Le Moal, M., Simon, H., and Piazza, P. V., 1995. Stress-induced sensitization and glucocorticoids. II. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress-induced corticosterone secretion. J. Neurosci. 15:7189–7195.

    PubMed  CAS  Google Scholar 

  48. Abrahamsen, G. C., and Carr, K. D., 1996. Effects of corticosteroid synthesis inhibitors on the sensitization of reward by food restriction. Brain Res. 726:39–48.

    Article  PubMed  CAS  Google Scholar 

  49. Carr, K. D., and Papadouka, V., 1994. The role of multiple opioid receptors in the potentiation of reward by food restriction. Brain Res. 639:253–260.

    Article  PubMed  CAS  Google Scholar 

  50. De Vry, J., Donselaar, I., and Van Ree, J. M., 1989. Food deprivation and acquisition of intravenous cocaine self-administration in rats: Effect of naltrexone and haloperidol. J. Pharm. Exp. Therap. 251:735–740.

    Google Scholar 

  51. Carr, K. D., and Simon, E. J., 1983. Effects of naloxone and its quaternary analogue on stimulation-induced feeding. Neuropharmacol. 22:127–130.

    Article  CAS  Google Scholar 

  52. Papadouka, V., and Carr, K. D., 1994. The role of multiple opioid receptors in the maintenance of stimulation-induced feeding. Brain Res. 639:42–48.

    Article  PubMed  CAS  Google Scholar 

  53. Carr, K. D., and Bak, T. H., 1990. Rostral and caudal ventricular infusion of antibodies to dynorphin A (1–17) and dynorphin A (1–8): effects on electrically-elicited feeding in the rat. Brain Res. 507:289–294.

    Article  PubMed  CAS  Google Scholar 

  54. Carr, K. D., 1996. Opioid receptor subtypes and stimulation-induced feeding. Pages 167–191,in Cooper, S. J., and Clifton, P. G. (eds.), Drug Receptor Subtypes and Ingestive Behavior, Academic Press, London.

    Google Scholar 

  55. Apfelbaum, M., and Mandenoff, A., 1991. Naltrexone suppresses hyperphagia induced in the rat by a highly palatable diet. Pharmacol. Biochem. Behav. 15:89–91.

    Article  Google Scholar 

  56. Kirkham, T. C., and Cooper, S. J., 1988. Attenuation of sham feeding by naloxone is stereospecific: evidence for opioid mediation of orosensory reward. Physiol. Behav. 43:845–847.

    Article  PubMed  CAS  Google Scholar 

  57. Lynch, W. C., 1986. Opiate blockade inhibits saccharin intake and blocks normal preference acquisition. Pharmacol. Biochem. Behav. 24:833–836.

    Article  PubMed  CAS  Google Scholar 

  58. Parker, L. A., Maier, S., Rennie, M., and Crebolder, J., 1992. Morphine- and naltrexone-induced modification of palatability: analysis by the taste reactivity test. Behav. Neurosci. 106:999–1010.

    Article  PubMed  CAS  Google Scholar 

  59. Rockwood, G. A., and Reid, L. D., 1982. Naloxone modifies sugar-water intake in rats drinking with open gastric fistulas. Physiol. Behav. 29:1175–1178.

    Article  PubMed  CAS  Google Scholar 

  60. Bals-Kubik, R., Herz, A., and Shippenberg, T. S., 1989. Evidence that the aversive effects of opioid antagonists and kappa agonists are centrally mediated. Psychopharmacol. 98:203–206.

    Article  CAS  Google Scholar 

  61. Bechara, A., and van der Kooy, D., 1987. Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacol. Biochem. Behav. 28:227–233.

    Article  PubMed  CAS  Google Scholar 

  62. Di Chiara, G., and Imperato, A., 1988. Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J. Pharmacol. Exp. Ther. 244:1067–1080.

    PubMed  Google Scholar 

  63. Spanagel, R., Herz, A., and Shippenberg, T. S., 1992. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc. Natl. Acad. Sci. 89:2046–2050.

    Article  PubMed  CAS  Google Scholar 

  64. Khazan, N., Young, G. A., and Calligaro, D., 1983. Self-administration of dynorphin-[1–13] and D-ALA-dynorphin-[1–11] (kappa opioid agonists) in morphine (mu opioid agonist)-dependent rats. Life Sci. 33:559–562.

    Article  PubMed  CAS  Google Scholar 

  65. Stein, L., and Belluzzi, J. D., 1989. Cellular investigations of behavioral reinforcement, Neurosci. Biobehav. Rev. 13:69–80.

    Article  PubMed  CAS  Google Scholar 

  66. Privette, T. H., and Terrian, D. M., 1995. Kappa opioid agonists produce anxiolytic-like behavior on the elevated plus-maze. Psychopharmacol. 118:444–450.

    Article  CAS  Google Scholar 

  67. Arjune, D., and Bodnar, R. J., 1990. Suppression of nocturnal, palatable and glucoprivic intake in rats by the κ opioid antagonist, nor-binaltorphimine. Brain Res. 534:313–316.

    Article  PubMed  CAS  Google Scholar 

  68. Leventhal, L., Kirkham, T. C., Cole, J. L., and Bodnar, R. J., 1995. Selective actions of central μ and κ opioid antagonists upon sucrose intake in sham-fed rats. Brain Res. 685:205–210.

    Article  PubMed  CAS  Google Scholar 

  69. Morley, J. E., and Levine, A. S., 1983. Involvement of dynorphin and the kappa opioid receptor in feeding. Peptides 4:797–800.

    Article  PubMed  CAS  Google Scholar 

  70. Carr, K. D., Papadouka, V., and Wolinsky, T. D., 1993. Norbinaltorphimine blocks the feeding but not the reinforcing effect of lateral hypothalamic electrical stimulation. Psychopharmacol. 111:345–350.

    Article  CAS  Google Scholar 

  71. Tsujii, S., Nakai, Y., Fukata, J., Koh, T., Takahashi, H., Usui, T., and Imura, H., 1986. Effects of food deprivation and high fat diet on opioid receptor binding in rat brain. Neurosci. Lett. 72: 169–173.

    Article  PubMed  CAS  Google Scholar 

  72. Tsujii, S., Nakai, Y., Koh, T., Takhashi, H., Usui, T., Ikeda, H., Matsuo, T., and Imura, H., 1986. Effect of food deprivation on opioid receptor binding in the brain of lean and fatty Zucker rats. Brain Res. 399:200–203.

    Article  PubMed  CAS  Google Scholar 

  73. Wolinsky, T. D., Carr, K. D., Hiller, J. M., and Simon, E. J., 1994. Effects of chronic food restriction on mu and kappa opioid binding in rat forebrain: a quantitative autoradiographic study. Brain Res. 656:274–280.

    Article  PubMed  CAS  Google Scholar 

  74. Wolinsky, T. D., Carr, K. D., Hiller, J. M., and Simon, E. J., 1996. Chronic food restriction alters mu and kappa opioid binding in the parabrachial nucleus of the rat: a quantitative autoradiographic study. Brain Res. 706:333–336.

    Article  PubMed  CAS  Google Scholar 

  75. Zukin, R. S., and Tempel, A., 1986. Neurochemical correlates of opiate receptor regulation. Biochem. Pharmacol. 35:1623–1627.

    Article  PubMed  CAS  Google Scholar 

  76. Yoburn, B., Billings, B., and Duttaroay, A., 1993. Opioid receptor regulation in mice. J. Pharmacol. Exper. Ther. 265:314–320.

    CAS  Google Scholar 

  77. Ferssiwi, A., Cardo, B., and Velley, L., 1987. Electrical self-stimulation in the parabrachial area is depressed after ibotenic acid lesion of the lateral hypothalamus. Behav. Brain Res. 25: 109–116.

    Article  PubMed  CAS  Google Scholar 

  78. Nishikawa, T., Fage, D., and Scatton, B., 1986. Evidence for, and nature of, the tonic inhibitory influence of habenulo-interpeduncular pathways upon cerebral dopaminergic transmission in the rat. Brain Res. 373:324–336.

    Article  PubMed  CAS  Google Scholar 

  79. Rolls, E. T., 1974. The neural basis of brain-stimulation reward. Prog. Neurobio. 3:71–160.

    Article  Google Scholar 

  80. Li, B.-H., Spector, A. C., and Rowland, N. E., 1994. Reversal of dexfenfluramine-induced anorexia and c-Fos/c-Jun expression by lesion in the lateral parabrachial nucleus. Brain Res. 640:255–267.

    Article  PubMed  CAS  Google Scholar 

  81. Yamamoto, T., Shimura, T., Sako, N., Yasoshima, Y., and Sakai, N., 1995. Neural substrates for conditioned taste aversion in the rat. Behav. Brain Res. 65:123–137.

    Article  Google Scholar 

  82. Berman, Y., Devi, L., and Carr, K. D., 1994. Effects of chronic food restriction on prodynorphin-derived peptides in rat brain regions. Brain Res. 664:49–53.

    Article  PubMed  CAS  Google Scholar 

  83. Berman, Y., Devi, L., and Carr, K. D., 1995. Effects of streptozotocin-induced diabetes on prodynorphin-derived peptides in rat brain regions. Brain Res. 685:129–134.

    Article  PubMed  CAS  Google Scholar 

  84. Uhl, G. R., and Nishimori, T., 1990. Neuropeptide gene expression and neural activity: assessing a working hypothesis in nucleus caudalis and dorsal horn neurons expressing preproenkephalin and preprodynorphin. Cell. and Molec. Neurobiol. 10:73–98.

    Article  CAS  Google Scholar 

  85. Berman, Y., Devi, L., Spangler, R., Kreek, M. J., and Carr, K. D., 1996. Chronic food restriction and streptozotocin-induced diabetes differentially alter prodynorphin mRNA levels in rat brain regions. Molec. Brain Res. (in press).

  86. Zardetto-Smith, A. M., Moga, M. M., Magnuson D. J., and Gray, T. S., 1988. Lateral hypothalamic dynorphinergic efferents to the amygdala and brainstem in the rat. Peptides 9:1121–1127.

    Article  PubMed  CAS  Google Scholar 

  87. Norgren, R., 1976. Taste pathways to hypothalamus and amygdala. J. Comp. Neurol. 166:17–30.

    Article  PubMed  CAS  Google Scholar 

  88. Yuan, C.-S., and Barber, W. D., 1991. Parabrachial nucleus: neuronal evoked responses to gastric vagal and greater splanchnic nerve stimulation. Brain Res. Bull. 27:797–803.

    Article  PubMed  CAS  Google Scholar 

  89. Moufid-Bellancourt, S., and Velley, L., 1994. Effects of morphine injection into the parabrachial area on saccharin preference: modulation by lateral hypothalamic neurons. Pharmacol. Biochem. Behav. 48:127–133.

    Article  PubMed  CAS  Google Scholar 

  90. Carr, K. D., Aleman, D. O., Bak, T. H., and Simon, E. J., 1991. Effects of parabrachial opioid antagonism on stimulation-induced feeding. Brain Res. 545:283–286.

    Article  PubMed  CAS  Google Scholar 

  91. Kasser, T. R., Deutch, A., and Martin, R. J., 1986. Uptake and utilization of metabolites in specific brain sites relative to feeding status. Physiol. Behav. 36:1161–1165.

    Article  PubMed  CAS  Google Scholar 

  92. Kasser, T. R., Harris, R. B. S., and Martin, R. J., 1989. Level of satiety: in vitro energymetabolism in brain during hypophagic and hyperphagic body weight recovery. Am. J. Physiol. 257: R1322-R1327.

    PubMed  CAS  Google Scholar 

  93. Bahjaoui-Bouhaddi, M., Fellmann, D., and Bugnon, C., 1994. Induction of Fos-immunoreactivity in prolactin-like containing neurons of the rat lateral hypothalamus after insulin treatment. Neurosci. Lett. 168:11–15.

    Article  PubMed  CAS  Google Scholar 

  94. Ritter, S., and Dinh, T. T., 1994. 2-Mercaptoacetate and 2-deoxy-d-glucose induce Fos-like immunoreactivity (Fos-li) in rat brain. Brain Res. 641:111–120.

    Article  PubMed  CAS  Google Scholar 

  95. Gardner, E. L., 1992. Brain reward mechanisms. Pages 70–99,in Lowinson, J. H., Ruiz, P., Millman, R. B., and Langrod, J. G. (eds.), Substance Abuse, A Comprehensive Textbook, Williams and Wilkins, Philadelphia.

    Google Scholar 

  96. Houdi, A. A., Bardo, M. T., and Van Loon, G. R., 1989. Opioid mediation of cocaine-induced hyperactivity and reinforcement. Brain Res. 497:195–198.

    Article  PubMed  CAS  Google Scholar 

  97. Menkens, K., Bilsky, E. J., Wild, K. D., Portoghese, P. S., Reid, L. D., and Porreca, F., 1992. Cocaine place preference is blocked by the δ-opioid receptor antagonist, naltrindole. Eur. J. Pharmacol. 219:345–346.

    Article  PubMed  CAS  Google Scholar 

  98. Stewart, J., 1984. Reinstatement of heroin and cocaine self-administration behavior in the rat by intracerebral application of morphine in the ventral tegmental area. Pharmacol. Biochem. Behav. 20:917–923.

    Article  PubMed  CAS  Google Scholar 

  99. Gerrits, M. A., Patkina, N., Zvartau, E. E., and van Ree, J. M., 1995. Opioid blockade attenuates acquisition and expression of cocaine-induced place preference conditioning in rats. Psychopharmacol. 119:92–98.

    Article  CAS  Google Scholar 

  100. Neisewander, J. L., and Bardo, M. T., 1987. Expression of morphine-conditioned hyperactivity is attenuated by naloxone and pimozide. Psychopharmacol. 93:314–319.

    CAS  Google Scholar 

  101. Volpicelli, J. R., Alterman, A. I., Hayashida, M., and O'Brien, C. P., 1992. Naltrexone in the treatment of alcohol dependence. Arch. Gen. Psychiat. 49:876–880.

    Article  PubMed  CAS  Google Scholar 

  102. Mitchell, J. E., Laine, D. E., Morley, J. E., and Levine, A. S., 1986. Naloxone but not CCK-8 may attenuate binge-eating behavior in patients with the bulimia syndrome. Biol. Psychiat. 21: 1399–1406.

    Article  PubMed  CAS  Google Scholar 

  103. Drewnowski, A., Krahn, D. D., Demitrack, M. A., Nairn, K., and Gosnell, B. A., 1992. Taste responses and preferences for sweet high-fat foods: evidence for opioid involvement. Physiol. Behav. 51:371–379.

    Article  PubMed  CAS  Google Scholar 

  104. Takemori, A. E., Loh, H. H., and Lee, N. M., 1993. Suppression by dynorphin A and [des-tyr1]dynorphin A peptides of the expression of opiate withdrawal and tolerance in morphine-dependent mice. J. Pharmacol. Exper. Therap. 266:121–124.

    CAS  Google Scholar 

  105. Yamamoto, T., Ohno, M., and Ueki, S., 1988. A selective κ-opioid agonist, U-50, 488H, blocks the development of tolerance to morphine analgesia in rats. Eur. J. Pharmacol. 156:173–176.

    Article  PubMed  CAS  Google Scholar 

  106. Suzuki, T., Narita, M., Takahashi, Y., Misawa, M., and Nagase, H., 1992. Effects of nor-binaltorphimine on the development of analgesic tolerance to and physical dependence on morphine. Eur. J. Pharmacol. 213:91–97.

    Article  PubMed  CAS  Google Scholar 

  107. Spanagel, R., and Shippenberg, T. S., 1993. Modulation of morphine-induced sensitization by endogenous κ opioid systems in the rat. Neurosci. Lett. 153:232–236.

    Article  PubMed  CAS  Google Scholar 

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Special issue dedicated to Dr. Eric J. Simon.

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Carr, K.D. Feeding, drug abuse, and the sensitization of reward by metabolic need. Neurochem Res 21, 1455–1467 (1996). https://doi.org/10.1007/BF02532386

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