OpenLB
Open Library of Bioscience
Advanced Search
British journal of pharmacology
Aug, 2017;174 (16): 2682-2695.

Cannabinoid CB /CB receptor agonists attenuate hyperactivity and body weight loss in a rat model of activity-based anorexia.

Maria Scherma, Valentina Satta, Roberto Collu, Maria Francesca Boi, Paolo Usai, Walter Fratta, Paola Fadda
Author Information
  1. Maria Scherma: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
  2. Valentina Satta: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
  3. Roberto Collu: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
  4. Maria Francesca Boi: Department of Internal Medicine, University of Cagliari, Cagliari, Italy.
  5. Paolo Usai: Department of Internal Medicine, University of Cagliari, Cagliari, Italy.
  6. Walter Fratta: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
  7. Paola Fadda: Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy. ORCID
PMID: 28561272 DOI: 10.1111/bph.13892

Abstract

BACKGROUND AND PURPOSE: anorexia nervosa (AN) is a serious psychiatric condition characterized by excessive body weight loss and disturbed perceptions of body shape and size, often associated with excessive physical activity. There is currently no effective drug-related therapy of this disease and this leads to high relapse rate. Clinical data suggest that a promising therapy to treat and reduce reoccurrence of AN may be based on the use of drugs that target the endocannabinoid (EC) system, which appears dysregulated in AN patients.
EXPERIMENTAL APPROACH: The activity-based anorexia (ABA) rodent model mimics the severe body weight loss and increased physical activity, as well as the neuroendocrine disturbances (i.e. hypoleptinaemia and hypercortisolaemia) in AN. This study investigated whether Cannabinoid agonists can effectively modify anorexic-like behaviours and neuroendocrine changes in rats subjected to a repeated ABA regime that mimics the human condition in which patients repeatedly undergo a recovery and illness cycle.
KEY RESULTS: Our data show that subchronic treatment with both the natural CB /CB receptor agonist Δ -tetrahydrocannabinol and the synthetic CB /CB receptor agonist CP-55,940 significantly reduced body weight loss and running wheel activity in ABA rats. These behavioural effects were accompanied by AN increase in leptin signalling and a decrease in plasma levels of corticosterone.
CONCLUSION AND IMPLICATIONS: Taken together, our results further demonstrate the involvement of the EC system in AN pathophysiology and that strategies which modulate EC signalling are useful to treat this disorder, specifically in patients where physical hyperactivity plays a central role in its progression and maintenance.

References

  1. J Neurosci. 2009 Sep 9;29(36):11078-88 [PMID: 19741114]
  2. Drug Alcohol Depend. 2014 Nov 1;144:12-41 [PMID: 25220897]
  3. Psychoneuroendocrinology. 2007 Jun;32(5):539-47 [PMID: 17462830]
  4. Int J Eat Disord. 2011 May;44(4):376-82 [PMID: 21472756]
  5. Int J Obes Relat Metab Disord. 1999 Apr;23 Suppl 3:S1-6 [PMID: 10367996]
  6. Arch Gen Psychiatry. 2011 Jul;68(7):724-31 [PMID: 21727255]
  7. Pharmacol Res. 2009 Aug;60(2):77-84 [PMID: 19559360]
  8. Br J Pharmacol. 2015 Jul;172(13):3189-93 [PMID: 25964986]
  9. Compr Psychiatry. 1997 Nov-Dec;38(6):321-6 [PMID: 9406737]
  10. Psychiatry Res. 2012 Dec 30;200(2-3):513-7 [PMID: 22703719]
  11. Psychoneuroendocrinology. 2016 May;67:171-81 [PMID: 26907996]
  12. Brain Res. 2003 Sep 5;983(1-2):144-51 [PMID: 12914975]
  13. Lancet Diabetes Endocrinol. 2014 Jul;2(7):581-92 [PMID: 24731664]
  14. Am J Clin Nutr. 1988 Jun;47(6):989-94 [PMID: 3376913]
  15. Int J Dev Neurosci. 2016 Nov;54:1-5 [PMID: 27521083]
  16. Eur Neuropsychopharmacol. 2011 Mar;21(3):274-81 [PMID: 21190812]
  17. Hippocampus. 2014 Dec;24(12):1421-9 [PMID: 24976385]
  18. J Neurosci. 2002 May 1;22(9):3326-31 [PMID: 11978807]
  19. Eur Neuropsychopharmacol. 2010 Sep;20(9):622-31 [PMID: 20471226]
  20. Curr Top Behav Neurosci. 2011;6:229-50 [PMID: 21243479]
  21. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1932-6 [PMID: 2308954]
  22. Neuropsychopharmacology. 2011 Jun;36(7):1349-58 [PMID: 21412227]
  23. Growth Horm IGF Res. 2015 Oct;25(5):247-52 [PMID: 26248813]
  24. Nat Med. 1995 Nov;1(11):1155-61 [PMID: 7584987]
  25. J Mol Endocrinol. 2005 Oct;35(2):381-90 [PMID: 16216917]
  26. J Comp Physiol Psychol. 1967 Dec;64(3):414-21 [PMID: 6082873]
  27. CNS Drug Rev. 2006 Summer;12(2):91-9 [PMID: 16958983]
  28. Eur J Pharmacol. 2003 Nov 7;480(1-3):133-50 [PMID: 14623357]
  29. Minerva Pediatr. 2014 Aug;66(4):237-48 [PMID: 25198558]
  30. J Neuroendocrinol. 2005 Nov;17(11):740-52 [PMID: 16219003]
  31. Physiol Behav. 2003 Nov;80(2-3):273-9 [PMID: 14637226]
  32. Nat Neurosci. 2005 May;8(5):585-9 [PMID: 15856067]
  33. Appetite. 2011 Jun;56(3):567-76 [PMID: 21281687]
  34. Br J Pharmacol. 2017 Aug;174(16):2682-2695 [PMID: 28561272]
  35. JAMA. 1999 Oct 27;282(16):1568-75 [PMID: 10546697]
  36. Br J Pharmacol. 2015 Jul;172(14):3461-71 [PMID: 26114403]
  37. Nutr Res Rev. 2014 Jun;27(1):172-85 [PMID: 24933167]
  38. PLoS One. 2013 Oct 21;8(10):e78251 [PMID: 24205172]
  39. Nature. 1996 Jul 18;382(6588):250-2 [PMID: 8717038]
  40. Br J Pharmacol. 2015 Dec;172(24):5744-869 [PMID: 26650439]
  41. Psychol Med. 2004 May;34(4):671-9 [PMID: 15099421]
  42. Mol Psychiatry. 1997 Jul;2(4):330-4 [PMID: 9246674]
  43. Behav Pharmacol. 2005 Sep;16(5-6):373-80 [PMID: 16148441]
  44. Behav Neurosci. 2013 Dec;127(6):878-89 [PMID: 24341712]
  45. J Comp Physiol Psychol. 1968 Aug;66(1):234-8 [PMID: 5672636]
  46. Psychoneuroendocrinology. 2009 May;34(4):620-4 [PMID: 19046818]
  47. Nat Rev Drug Discov. 2008 May;7(5):438-55 [PMID: 18446159]
  48. Biol Psychiatry. 2005 Jul 15;58(2):165-71 [PMID: 16038687]
  49. Psychopharmacology (Berl). 2002 Dec;164(4):407-15 [PMID: 12457271]
  50. Psychopharmacology (Berl). 2008 Aug;199(3):313-29 [PMID: 18317734]
  51. Biochem Cell Biol. 2006 Apr;84(2):207-14 [PMID: 16609702]
  52. Br J Pharmacol. 2010 Aug;160(7):1577-9 [PMID: 20649561]
  53. J Neurochem. 1999 Dec;73(6):2447-59 [PMID: 10582605]
  54. Physiol Behav. 1989 Feb;45(2):403-5 [PMID: 2756029]
  55. Brain Res. 2017 Jan 1;1654(Pt B):102-115 [PMID: 26779892]
  56. J Clin Endocrinol Metab. 2003 Nov;88(11):5169-74 [PMID: 14602745]
  57. Neuroscience. 2009 Nov 10;163(4):1192-200 [PMID: 19607884]
  58. Int J Eat Disord. 2014 Jan;47(1):18-23 [PMID: 24105610]
  59. J Vis Exp. 2015 Oct 22;(105):e52927 [PMID: 26555618]
  60. Psychoneuroendocrinology. 2009 Apr;34(3):436-45 [PMID: 19028018]
  61. World Rev Nutr Diet. 2015;111:169-73 [PMID: 25418408]
  62. Psychopharmacology (Berl). 1999 Apr;143(3):315-7 [PMID: 10353436]
  63. Nat Med. 1995 Dec;1(12):1311-4 [PMID: 7489415]
  64. Nutr Rev. 2016 May;74(5):301-11 [PMID: 27052638]
  65. Int J Eat Disord. 2013 May;46(4):289-301 [PMID: 23354987]
  66. Neuroscience. 2012 Mar 1;204:5-16 [PMID: 22214537]
  67. J Nutr. 1993 Jul;123(7):1217-25 [PMID: 8320563]
  68. Physiol Behav. 2003 Jun;79(1):25-37 [PMID: 12818707]
  69. Behav Neurosci. 1997 Feb;111(1):195-205 [PMID: 9109638]
  70. Biol Psychiatry. 2011 Oct 15;70(8):777-84 [PMID: 21718968]
  71. Eur Eat Disord Rev. 2015 Sep;23(5):333-44 [PMID: 26087044]
  72. J Eat Disord. 2015 Mar 31;3:11 [PMID: 25834735]
  73. Compr Psychiatry. 2014 Nov;55(8):1773-84 [PMID: 25214371]
  74. Eur J Nucl Med Mol Imaging. 2014 Feb;41(2):308-21 [PMID: 24006151]
  75. Int J Eat Disord. 1997 Dec;22(4):339-60 [PMID: 9356884]
  76. Biol Psychiatry. 2007 Feb 1;61(3):348-58 [PMID: 16815322]
  77. Peptides. 2010 Oct;31(10):1912-9 [PMID: 20600421]
  78. Nucleic Acids Res. 2016 Jan 4;44(D1):D1054-68 [PMID: 26464438]
  79. Curr Psychiatry Rep. 2012 Aug;14(4):406-14 [PMID: 22644309]
  80. Mol Psychiatry. 2000 Sep;5(5):476-81 [PMID: 11032380]
  81. Pharmacol Biochem Behav. 1995 Mar;50(3):405-12 [PMID: 7617679]
  82. Neuropsychopharmacology. 2005 Jun;30(6):1216-21 [PMID: 15841111]

MeSH Term

Animals
Anorexia
Body Weight
Cannabinoid Receptor Agonists
Corticosterone
Cyclohexanols
Disease Models, Animal
Dronabinol
Eating
Female
Hyperkinesis
Leptin
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2
Weight Loss

Chemicals

Cannabinoid Receptor Agonists
Cyclohexanols
Leptin
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2
Dronabinol
3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol
Corticosterone
Journal Article
Article has an altmetric score of 7

Word Cloud

Created with Highcharts 10.0.0ANbodyweightlossphysicalactivityECpatientsABACB/CBreceptorANDconditionexcessivetherapydatatreatsystemactivity-basedanorexiamodelmimicsneuroendocrineagonistsratsagonistsignallinghyperactivityBACKGROUNDPURPOSE:Anorexianervosaseriouspsychiatriccharacterizeddisturbedperceptionsshapesizeoftenassociatedcurrentlyeffectivedrug-relateddiseaseleadshighrelapserateClinicalsuggestpromisingreducereoccurrencemaybasedusedrugstargetendocannabinoidappearsdysregulatedEXPERIMENTALAPPROACH:rodentsevereincreasedwelldisturbancesiehypoleptinaemiahypercortisolaemiastudyinvestigatedwhethercannabinoidcaneffectivelymodifyanorexic-likebehaviourschangessubjectedrepeatedregimehumanrepeatedlyundergorecoveryillnesscycleKEYRESULTS:showsubchronictreatmentnaturalΔ-tetrahydrocannabinolsyntheticCP-55940significantlyreducedrunningwheelbehaviouraleffectsaccompaniedincreaseleptindecreaseplasmalevelscorticosteroneCONCLUSIONIMPLICATIONS:TakentogetherresultsdemonstrateinvolvementpathophysiologystrategiesmodulateusefuldisorderspecificallyplayscentralroleprogressionmaintenanceCannabinoidattenuaterat

Similar Articles

Cited By (17)