An Orexin Hotspot in Ventral Pallidum Amplifies Hedonic ‘Liking’ for Sweetness

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Abstract

Orexin (hypocretin) is implicated in stimulating appetite as well as arousal, and in both food reward and drug reward. The ventral pallidum (VP) receives orexin projections from lateral hypothalamus neurons (LH), and orexin terminals are especially dense in the posterior half of VP, which is also the location of an opioid hedonic hotspot. The VP hotspot is a roughly cubic-millimeter site where mu opioid stimulation can amplify the hedonic impact of sweetness, expressed as an increase in ‘liking’ reactions to sucrose taste. The anatomical overlap in posterior VP between opioid hotspot and orexin inputs raises the possibility that the hedonic hotspot might allow orexin to amplify ‘liking’ too. We examined whether microinjections of orexin-A into the VP hotspot enhance the hedonic impact of sucrose, as assessed via affective taste reactivity measures of ‘liking’ reactions, and additionally compared effects at nearby sites in adjacent LH and extended amygdala. Taste reactivity results indicated that orexin stimulation specifically in the VP hotspot nearly doubled the magnitude of positive ‘liking’ reactions elicited by the taste of sucrose. Mapping results for localization of function, aided by Fos plume measures of the local spread of orexin impact, suggested that hedonic enhancement was generated by essentially the same cubic-millimeter of posterior VP previously identified as the opioid hotspot. By contrast, microinjection sites in the anterior half of VP, or in LH or extended amygdala, generally failed to produce any hedonic enhancement. We conclude that an orexin hedonic hotspot exists in posterior VP, with similar boundaries to the opioid hotspot. An orexin hedonic hotspot may permit regulatory hypothalamic circuitry to make foods more ‘liked’ during hunger by acting through VP. Dysfunction in a VP orexin hotspot in addiction or mood disorders might also contribute to some types of affective psychopathology.

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References

  1. Aristotle (350BC) (2009) The Nicomachean ethics. Oxford University Press: Oxford, UK.

  2. Aston-Jones G, Harris GC (2004). Brain substrates for increased drug seeking during protracted withdrawal. Neuropharmacology 47: 167–179.

  3. Aston-Jones G, Smith RJ, Sartor GC, Moorman DE, Massi L, Tahsili-Fahadan P et al (2010). Lateral hypothalamic orexin/hypocretin neurons: a role in reward-seeking and addiction. Brain Res 1314: 74–90.

  4. Baldo BA, Daniel RA, Berridge CW, Kelley AE (2003). Overlapping distributions of orexin/hypocretin- and dopamine-beta-hydroxylase immunoreactive fibers in rat brain regions mediating arousal, motivation, and stress. J Comp Neurol 464: 220–237.

  5. Beaver J, Lawrence A, van Ditzhuijzen J, Davis M, Woods A, Calder A (2006). Individual differences in reward drive predict neural responses to images of food. J Neurosci 26: 5160–5166.

  6. Berridge KC (2000). Measuring hedonic impact in animals and infants: microstructure of affective taste reactivity patterns. Neurosci Biobehav Rev 24: 173–198.

  7. Berthoud H-R, Lenard NR, Shin AC (2011). Food reward, hyperphagia, and obesity. Am J Physiol 300: R1266–R1277.

  8. Berthoud HR, Morrison C (2008). The brain, appetite, and obesity. Annu Rev Psychol 59: 55–92.

  9. Borgland SL, Chang S-J, Bowers MS, Thompson JL, Vittoz N, Floresco SB et al (2009). Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. J Neurosci 29: 11215–11225.

  10. Cabanac M (1971). Physiological role of pleasure. Science 173: 1103–1107.

  11. Choi DL, Davis JF, Fitzgerald ME, Benoit SC (2010). The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats. Neuroscience 167: 11–20.

  12. España R, Calipari ES (2012). Hypocretin/orexin regulation of dopamine signaling: implications for reward and reinforcement mechanisms. Front Behav Neurosci 6: 54.

  13. Gao Q, Horvath TL (2007). Neurobiology of feeding and energy expenditure. Annu Rev Neurosci 30: 367–398.

  14. Gao Q, Horvath TL (2008). Neuronal control of energy homeostasis. FEBS Lett 582: 132–141.

  15. Grill HJ, Norgren R (1978). The taste reactivity test. I. Mimetic responses to gustatory stimuli in neurologically normal rats. Brain Res 143: 263–279.

  16. Groenewegen HJ, Berendse HW, Haber SN (1993). Organization of the output of the ventral striatopallidal system in the rat: ventral pallidal efferents. Neuroscience 57: 113–142.

  17. Groenewegen HJ, Wright CI, Beijer AV, Voorn P (1999). Convergence and segregation of ventral striatal inputs and outputs. Ann N Y Acad Sci 877: 49–63.

  18. Haber SN, Knutson B (2010). The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35: 4–26.

  19. Haber SN, Lynd-Balta E, Mitchell SJ (1993). The organization of the descending ventral pallidal projections in the monkey. J Comparative Neurol 329: 111–128.

  20. Harris GC, Aston-Jones G (2006). Arousal and reward: a dichotomy in orexin function. Trends Neurosci 29: 571–577.

  21. Harris GC, Wimmer M, Aston-Jones G (2005). A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437: 556–559.

  22. Heimer L, Van Hoesen GW, Trimble M, Zahm DS (2008) Anatomy of Neuropsychiatry: The New Anatomy of the Basal Forebrain and its Implications for Neuropsychiatric Illness. Elsevier: Academic Press: Amsterdam.

  23. Ho C-Y (2010). The Ventral Pallidum as a Limbic Pleasure Generator. PhD Dissertation at The University of Michigan, Ann Arbor, MI, USA.

  24. Jupp B, Krivdic B, Krstew E, Lawrence AJ (2011). The orexin(1) receptor antagonist SB-334867 dissociates the motivational properties of alcohol and sucrose in rats. Brain Res 1391: 54–59.

  25. Kalivas PW, Nakamura M (1999). Neural systems for behavioral activation and reward. Cur Opin Neurobiol 9: 223–227.

  26. Kelley AE, Baldo BA, Pratt WE (2005). A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and food reward. J Comp Neurol 493: 72–85.

  27. Kim AK, Brown RM, Lawrence AJ (2012). The role of orexins/hypocretins in alcohol use and abuse: an appetitive-reward relationship. Front Behav Neurosci 6: 78.

  28. Kringelbach ML (2005). The human orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci 6: 691–702.

  29. Kupchik YM, Kalivas PW (2012). The rostral subcommissural ventral pallidum is a mix of ventral pallidal neurons and neurons from adjacent areas: an electrophysiological study. Brain Structure Function (doi:10.1007/s00429-012-0471-9) .

  30. Mahler SV, Smith KS, Berridge KC (2007). Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances 'liking' of a sweet reward. Neuropsychopharmacology 32: 2267–2278.

  31. Mahler SV, Smith RJ, Moorman DE, Sartor GC, Aston-Jones G (2012). Multiple roles for orexin/hypocretin in addiction. Prog Brain Res 198: 79–121.

  32. Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M et al (2001). Differential expression of orexin receptors 1 and 2 in the rat brain. J Comparative Neurol 435: 6–25.

  33. Napier TC, Mickiewicz AL (2010). The role of the ventral pallidum in psychiatric disorders. Neuropsychopharmacology 35: 337–337.

  34. Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates 4th edn. Academic Press: New York.

  35. Peciña S, Berridge KC (2005). Hedonic hot spot in nucleus accumbens shell: Where do mu-opioids cause increased hedonic impact of sweetness? J Neurosci 25: 11777–11786.

  36. Richard JM, Berridge KC (2011). Nucleus accumbens dopamine/glutamate interaction switches modes to generate desire versus dread: d1 alone for appetitive eating but D1 and D2 together for fear. J Neurosci 31: 12866–12879.

  37. Robinson MJF, Berridge KC in press (2013). Instant transformation of learned repulsion into motivational ‘wanting’. Curr Biol 23: 282–289.

  38. Shimura T, Imaoka H, Yamamoto T (2006). Neurochemical modulation of ingestive behavior in the ventral pallidum. Eur J Neurosci 23: 1596–1604.

  39. Smith KS, Berridge KC (2005). The ventral pallidum and hedonic reward: neurochemical maps of sucrose ‘liking’ and food intake. J Neurosci 25: 8637–8649.

  40. Smith KS, Berridge KC (2007). Opioid limbic circuit for reward: interaction between hedonic hotspots of nucleus accumbens and ventral pallidum. J Neurosci 27: 1594–1605.

  41. Smith KS, Berridge KC, Aldridge JW (2011). Disentangling pleasure from incentive salience and learning signals in brain reward circuitry. Proc Natl Acad Sci USA 108: E255–E264.

  42. Smith KS, Mahler SV, Pecina S, Berridge KC (2010a). Hedonic Hotspots: Generating Sensory Pleasure in the Brain. In: Kringelbach ML, Berridge KC, eds. Pleasures of the Brain. Oxford University Press: Oxford, UK. pp 27–49.

  43. Smith KS, Tindell AJ, Aldridge JW, Berridge KC (2009). Ventral pallidum roles in reward and motivation. Behav Brain Res 196: 155–167.

  44. Smith RJ, Tahsili-Fahadan P, Aston-Jones G (2010b). Orexin/hypocretin is necessary for context-driven cocaine-seeking. Neuropharmacology 58: 179–184.

  45. Steiner JE (1973). The gustofacial response: observation on normal and anencephalic newborn infants. Symposium on Oral Sensation and Perception 4: 254–278.

  46. Steiner JE, Glaser D, Hawilo ME, Berridge KC (2001). Comparative expression of hedonic impact: affective reactions to taste by human infants and other primates. Neurosci Biobehav Rev 25: 53–74.

  47. Stoeckel LE, Weller RE, Cook EW 3rd, Twieg DB, Knowlton RC, Cox JE (2008). Widespread reward-system activation in obese women in response to pictures of high-calorie foods. Neuroimage 41: 636–647.

  48. Stratford TR, Wirtshafter D (2012). Lateral hypothalamic involvement in feeding elicited from the ventral pallidum. Eur J Neurosci 37: 648–653.

  49. Thompson JL, Borgland SL (2011). A role for hypocretin/orexin in motivation. Behav Brain Res 217: 446–453.

  50. Thompson RH, Swanson LW (2010). Hypothesis-driven structural connectivity analysis supports network over hierarchical model of brain architecture. Proc Natl Acad Sci USA 107: 15235–15239.

  51. Thorpe AJ, Kotz CM (2005). Orexin A in the nucleus accumbens stimulates feeding and locomotor activity. Brain Res 1050: 156–162.

  52. Tindell AJ, Smith KS, Berridge KC, Aldridge JW (2009). Dynamic computation of incentive salience: ‘wanting’ what was never ‘liked’. J Neurosci 29: 12220–12228.

  53. Tindell AJ, Smith KS, Pecina S, Berridge KC, Aldridge JW (2006). Ventral pallidum firing codes hedonic reward: when a bad taste turns good. J Neurophysiol 96: 2399–2409.

  54. Valenstein ES, Cox VC, Kakolewski JW (1970). Reexamination of the role of the hypothalamus in motivation. Psychol Rev 77: 16–31.

  55. Wassum KM, Ostlund SB, Maidment NT, Balleine BW (2009). Distinct opioid circuits determine the palatability and the desirability of rewarding events. Proc Natl Acad Sci 106: 12512–12517.

  56. Zahm DS, Parsley KP, Schwartz ZM, Cheng AY (2013). On lateral septum-like characteristics of outputs from the accumbal hedonic ‘hotspot’ of Peciña and Berridge with commentary on the transitional nature of basal forebrain ‘boundaries’. J Comp Neurol 521: 50–68.

  57. Zahm DS, Williams E, Wohltmann C (1996). Ventral striatopallidothalamic projection: IV. Relative involvements of neurochemically distinct subterritories in the ventral pallidum and adjacent parts of the rostroventral forebrain. J Comp Neurol 364: 340–362.

  58. Zheng H, Patterson L, Berthoud H (2007). Orexin signaling in the ventral tegmental area is required for high-fat appetite induced by opioid stimulation of the nucleus accumbens. J Neurosci 27: 11075–11082.

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Acknowledgements

This research was supported by MH63649 and DA015188 grants from the NIH. We thank Brian Baldo and colleagues for allowing us to redraw parts of Figure 3 inset derived from Baldo et al (2003) Figure 1 panels g and h (orexin terminal distribution in VP), and thank Aaron Garcia for redrawing the inset.

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Correspondence to Chao-Yi Ho or Kent C Berridge.

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Keywords

  • ventral pallidum
  • lateral hypothalamus
  • pleasure
  • addiction
  • reward
  • eating disorders

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