The anxiolytic effects of cannabidiol in chronically stressed mice are mediated by the endocannabinoid system: Role of neurogenesis and dendritic remodeling

Neuropharmacology

Volumn 135, Issue , 2018, Pages 22-33

  Fogaça, Manoela V ^a,b   Campos, Alline C ^a   Coelho, Ludmila D ^a   Duman, Ronald S ^b   Guimarães, Francisco S ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anxiety; Cannabidiol; CB1 receptor; CB2 receptor; Dendritic spines; Neurogenesis

Indexed keywords

CANNABIDIOL; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; DISKS LARGE HOMOLOG 4; FATTY ACID AMIDASE; GLYCOGEN SYNTHASE KINASE 3BETA; METABOTROPIC RECEPTOR 1; PHOSPHOPROTEIN; PROTEIN KINASE B; SEROTONIN 1A RECEPTOR; SYNAPSIN IA; SYNAPSIN IB; UNCLASSIFIED DRUG; 1 (2,4 DICHLOROPHENYL) 5 (4 IODOPHENYL) 4 METHYL N (1 PIPERIDYL) 1H PYRAZOLE 3 CARBOXAMIDE; AMIDASE; ANXIOLYTIC AGENT; DLG4 PROTEIN, MOUSE; FATTY-ACID AMIDE HYDROLASE; GSK3B PROTEIN, MOUSE; INDOLE DERIVATIVE; IODOPRAVADOLINE; METABOTROPIC GLUTAMATE RECEPTOR TYPE 1; METABOTROPIC RECEPTOR; N-(2-(4-(2-METHOXYPHENYL)-1-PIPERAZINYL)ETHYL)-N-(2-PYRIDINYL)CYCLOHEXANECARBOXAMIDE; PIPERAZINE DERIVATIVE; PIPERIDINE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; SEROTONIN 1 ANTAGONIST; SYNAPSIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CHRONIC UNPREDICTABLE STRESS; CONTROLLED STUDY; DENDRITE; DENTATE GYRUS; DRUG EFFECT; ELEVATED PLUS MAZE TEST; HIPPOCAMPUS; INTRACELLULAR SIGNALING; MALE; MOUSE; NERVOUS SYSTEM DEVELOPMENT; NONHUMAN; NOVELTY SUPPRESSED FEEDING TEST; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANQUILIZING ACTIVITY; ANIMAL; ANIMAL BEHAVIOR; ANTAGONISTS AND INHIBITORS; CYTOLOGY; MENTAL STRESS; METABOLISM; NERVE CELL PLASTICITY; PREVENTION AND CONTROL;

AMIDOHYDROLASES; ANIMALS; ANTI-ANXIETY AGENTS; BEHAVIOR, ANIMAL; CANNABIDIOL; DISKS LARGE HOMOLOG 4 PROTEIN; GLYCOGEN SYNTHASE KINASE 3 BETA; HIPPOCAMPUS; INDOLES; MALE; MICE; NEUROGENESIS; NEURONAL PLASTICITY; PIPERAZINES; PIPERIDINES; PROTO-ONCOGENE PROTEINS C-AKT; PYRAZOLES; PYRIDINES; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; RECEPTORS, METABOTROPIC GLUTAMATE; SEROTONIN 5-HT1 RECEPTOR ANTAGONISTS; STRESS, PSYCHOLOGICAL; SYNAPSINS;

EID: 85043367812     PISSN: 00283908     EISSN: 18737064     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2018.03.001     Document Type: Article

References (76)

1. Barnes, M.P., Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain. Expet Opin. Pharmacother. 7 (2006), 607–615.
2. Bianchi, M., Heidbreder, C., Crespi, F., Cytoskeletal changes in the hippocampus following restraint stress: role of serotonin and microtubules. Synapse 49 (2003), 188–194.
3. Bisogno, T., Hanus, L., De Petrocellis, L., Tchilibon, S., Ponde, D.E., Brandi, I., Moriello, A.S., Davis, J.B., Mechoulam, R., Di Marzo, V., Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br. J. Pharmacol. 134 (2001), 845–852.
4. Bortolato, M., Mangieri, R.A., Fu, J., Kim, J.H., Arguello, O., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Piomelli, D., Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol. Psychiatr. 62 (2007), 1103–1110.
5. Bremner, J.D., Vythilingam, M., Vermetten, E., Nazeer, A., Adil, J., Khan, S., Staib, L.H., Charney, D.S., Reduced volume of orbitofrontal cortex in major depression. Biol. Psychiatr. 51 (2002), 273–279.
6. Campbell, S., Marriott, M., Nahmias, C., MacQueen, G.M., Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am. J. Psychiatr. 161 (2004), 598–607.
7. Campos, A.C., Guimaraes, F.S., Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berlin) 199 (2008), 223–230.
8. Campos, A.C., Ferreira, F.R., Guimaraes, F.S., Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. J. Psychiatr. Res. 46 (2012), 1501–1510.
9. Campos, A.C., de Paula Soares, V., Carvalho, M.C., Ferreira, F.R., Vicente, M.A., Brandao, M.L., Zuardi, A.W., Zangrossi, H. Jr., Guimaraes, F.S., Involvement of serotonin-mediated neurotransmission in the dorsal periaqueductal gray matter on cannabidiol chronic effects in panic-like responses in rats. Psychopharmacology (Berlin) 226 (2013), 13–24.
10. Campos, A.C., Ortega, Z., Palazuelos, J., Fogaca, M.V., Aguiar, D.C., Diaz-Alonso, J., Ortega-Gutierrez, S., Vazquez-Villa, H., Moreira, F.A., Guzman, M., Galve-Roperh, I., Guimaraes, F.S., The anxiolytic effect of cannabidiol on chronically stressed mice depends on hippocampal neurogenesis: involvement of the endocannabinoid system. Int. J. Neuropsychopharmacol. 16 (2013), 1407–1419.
11. Campos, A.C., Fogaca, M.V., Sonego, A.B., Guimaraes, F.S., Cannabidiol, neuroprotection and neuropsychiatric disorders. Pharmacol. Res. 112 (2016), 119–127.
12. Christian, K.M., Song, H., Ming, G.L., Functions and dysfunctions of adult hippocampal neurogenesis. Annu. Rev. Neurosci. 37 (2014), 243–262.
13. Cruceanu, C., Alda, M., Grof, P., Rouleau, G.A., Turecki, G., Synapsin II is involved in the molecular pathway of lithium treatment in bipolar disorder. PLoS One, 7, 2012 e32680.
14. David, D.J., Samuels, B.A., Rainer, Q., Wang, J.W., Marsteller, D., Mendez, I., Drew, M., Craig, D.A., Guiard, B.P., Guilloux, J.P., Artymyshyn, R.P., Gardier, A.M., Gerald, C., Antonijevic, I.A., Leonardo, E.D., Hen, R., Neurogenesis-dependent and -independent effects of fluoxetine in an animal model of anxiety/depression. Neuron 62:4 (2009), 479–493.
15. David, D.J., Wang, J., Samuels, B.A., Rainer, Q., David, I., Gardier, A.M., Hen, R., Implications of the functional integration of adult-born hippocampal neurons in anxiety-depression disorders. Neuroscientist 16:5 (2010), 578–591.
16. De Petrocellis, L., Ligresti, A., Moriello, A.S., Allara, M., Bisogno, T., Petrosino, S., Stott, C.G., Di Marzo, V., Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br. J. Pharmacol. 163 (2011), 1479–1494.
17. Dhopeshwarkar, A., Mackie, K., CB2 Cannabinoid receptors as a therapeutic target-what does the future hold?. Mol. Pharmacol. 86:4 (2014), 430–437.
18. Duman, R.S., Aghajanian, G.K., Neurobiology of rapid acting antidepressants: role of BDNF and GSK-3beta. Neuropsychopharmacology, 39, 2014, 233.
19. Duman, C.H., Duman, R.S., Spine synapse remodeling in the pathophysiology and treatment of depression. Neurosci. Lett. 601 (2015), 20–29.
20. Dyck, B.A., Beyaert, M.G., Ferro, M.A., Mishra, R.K., Medial prefrontal cortical synapsin II knock-down induces behavioral abnormalities in the rat: examining synapsin II in the pathophysiology of schizophrenia. Schizophr. Res. 130 (2011), 250–259.
21. Esposito, G., Scuderi, C., Valenza, M., Togna, G.I., Latina, V., De Filippis, D., Cipriano, M., Carratu, M.R., Iuvone, T., Steardo, L., Cannabidiol reduces Abeta-induced neuroinflammation and promotes hippocampal neurogenesis through PPARgamma involvement. PLoS One, 6, 2011 e28668.
22. Fogaca, M.V., Reis, F.M., Campos, A.C., Guimaraes, F.S., Effects of intra-prelimbic prefrontal cortex injection of cannabidiol on anxiety-like behavior: involvement of 5HT1A receptors and previous stressful experience. Eur. Neuropsychopharmacol 24 (2014), 410–419.
23. Fogaça, M.V., C, A., Guimarães, F.S., Cannabidiol and 5HT1A receptors. RV, P., (eds.) Neuropathology of Drug Addictions and Substance Misuse, 2016, Academic Press, London, 749–759.
24. Garcia-Gutierrez, M.S., Manzanares, J., The cannabinoid CB1 receptor is involved in the anxiolytic, sedative and amnesic actions of benzodiazepines. J. Psychopharmacol. 24 (2010), 757–765.
25. Gould, T.D., Zarate, C.A., Manji, H.K., Glycogen synthase kinase-3: a target for novel bipolar disorder treatments. J. Clin. Psychiatr. 65:1 (2004), 10–21.
26. Griebel, G., Rodgers, R.J., Perrault, G., Sanger, D.J., Behavioural profiles in the mouse defence test battery suggest anxiolytic potential of 5-HT(1A) receptor antagonists. Psychopharmacology (Berlin) 144 (1999), 121–130.
27. Griebel, G., Rodgers, R.J., Perrault, G., Sanger, D.J., The effects of compounds varying in selectivity as 5-HT(1A) receptor antagonists in three rat models of anxiety. Neuropharmacology 39 (2000), 1848–1857.
28. Guimaraes, F.S., Chiaretti, T.M., Graeff, F.G., Zuardi, A.W., Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berlin) 100 (1990), 558–559.
29. Hill, M.N., Kambo, J.S., Sun, J.C., Gorzalka, B.B., Galea, L.A., Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviours. Eur. J. Neurosci. 24 (2006), 1845–1849.
30. Hill, M.N., Carrier, E.J., McLaughlin, R.J., Morrish, A.C., Meier, S.E., Hillard, C.J., Gorzalka, B.B., Regional alterations in the endocannabinoid system in an animal model of depression: effects of concurrent antidepressant treatment. J. Neurochem. 106 (2008), 2322–2336.
31. Hill, M.N., Carrier, E.J., Ho, W.S., Shi, L., Patel, S., Gorzalka, B.B., Hillard, C.J., Prolonged glucocorticoid treatment decreases cannabinoid CB1 receptor density in the hippocampus. Hippocampus 18:2 (2008), 221–226.
32. Hill, M.N., Hillard, C.J., McEwen, B.S., Alterations in corticolimbic dendritic morphology and emotional behavior in cannabinoid CB1 receptor-deficient mice parallel the effects of chronic stress. Cerebr. Cortex 21 (2011), 2056–2064.
33. Hill, M.N., Kumar, S.A., Filipski, S.B., Iverson, M., Stuhr, K.L., Keith, J.M., Cravatt, B.F., Hillard, C.J., Chattarji, S., McEwen, B.S., Disruption of fatty acid amide hydrolase activity prevents the effects of chronic stress on anxiety and amygdalar microstructure. Mol. Psychiatr. 18 (2013), 1125–1135.
34. Ichikawa, J., Meltzer, H.Y., Valproate and carbamazepine increase prefrontal dopamine release by 5-HT1A receptor activation. Eur. J. Pharmacol. 380 (1999), R1–R3.
35. Ichikawa, J., Meltzer, H.Y., The effect of serotonin(1A) receptor agonism on antipsychotic drug-induced dopamine release in rat striatum and nucleus accumbens. Brain Res. 858 (2000), 252–263.
36. Jin, K., Xie, L., Kim, S.H., Parmentier-Batteur, S., Sun, Y., Mao, X.O., Childs, J., Greenberg, D.A., Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Mol. Pharmacol. 66 (2004), 204–208.
37. Kang, E., Wen, Z., Song, H., Christian, K.M., Ming, G.L., Adult neurogenesis and psychiatric disorders. Cold Spring Harb Perspect Biol, 8(9), 2016, 1.
38. Kempermann, G., The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for?. Trends Neurosci. 31 (2008), 163–169.
39. Komaki, A., Hashemi-Firouzi, N., Shojaei, S., Souri, Z., Heidari, S., Shahidi, S., Study the effect of endocannabinoid system on rat behavior in elevated plus-maze. Basic Clin. Neurosci. 6 (2015), 147–153.
40. Lee, S., Kim, D.H., Yoon, S.H., Ryu, J.H., Sub-chronic administration of rimonabant causes loss of antidepressive activity and decreases doublecortin immunoreactivity in the mouse hippocampus. Neurosci. Lett. 467 (2009), 111–116.
41. Leo, A., Russo, E., Elia, M., Cannabidiol and epilepsy: rationale and therapeutic potential. Pharmacol. Res. 107 (2016), 85–92.
42. Leweke, F.M., Piomelli, D., Pahlisch, F., Muhl, D., Gerth, C.W., Hoyer, C., Klosterkotter, J., Hellmich, M., Koethe, D., Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl. Psychiatry, 2, 2012, e94.
43. Li, X., Jope, R.S., Is glycogen synthase kinase-3 a central modulator in mood regulation?. Neuropsychopharmacology 35:11 (2010), 2143–2154.
44. Li, Y., Kim, J., Deletion of CB2 cannabinoid receptors reduces synaptic transmission and long-term potentiation in the mouse hippocampus. Hippocampus 26 (2016), 275–281.
45. Licznerski, P., Duman, R.S., Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression. Neuroscience 251 (2013), 33–50.
46. Lomazzo, E., Bindila, L., Remmers, F., Lerner, R., Schwitter, C., Hoheisel, U., Lutz, B., Therapeutic potential of inhibitors of endocannabinoid degradation for the treatment of stress-related hyperalgesia in an animal model of chronic pain. Neuropsychopharmacology 40 (2015), 488–501.
47. Magarinos, A.M., Verdugo, J.M., McEwen, B.S., Chronic stress alters synaptic terminal structure in hippocampus. Proc. Natl. Acad. Sci. U. S. A. 94 (1997), 14002–14008.
48. Monory, K., Polack, M., Remus, A., Lutz, B., Korte, M., Cannabinoid CB1 receptor calibrates excitatory synaptic balance in the mouse hippocampus. J. Neurosci. 35 (2015), 3842–3850.
49. Mundt, C., Reck, C., Backenstrass, M., Kronmüller, K., Fiedler, P., Reconfirming the role of life events for the timing of depressive episodes. A two-year prospective follow-up study. J. Affect. Disord. 59:1 (2000), 23–30.
50. O'Brien, L.D., Wills, K.L., Segsworth, B., Dashney, B., Rock, E.M., Limebeer, C.L., Parker, L.A., Effect of chronic exposure to rimonabant and phytocannabinoids on anxiety-like behavior and saccharin palatability. Pharmacol. Biochem. Behav. 103 (2013), 597–602.
51. O'Leary, O., Nolan, Y., Glycogen synthase kinase-3 as a therapeutic target for cognitive dysfunction in neuropsychiatric disorders. CNS Drugs 29 (2015), 1–15.
52. Ortega, F., Pérez-Sen, R., Morente, V., Delicado, E.G., Miras-Portugal, M.T., P2X7, NMDA and BDNF receptors converge on GSK3 phosphorylation and cooperate to promote survival in cerebellar granule neurons. Cell. Mol. Life Sci. 67:10 (2010), 1723–1733.
53. Ozaita, A., Puighermanal, E., Maldonado, R., Regulation of PI3K/Akt/GSK-3 pathway by cannabinoids in the brain. J. Neurochem. 102 (2007), 1105–1114.
54. Pardo, M., Abrial, E., Jope, R.S., Beurel, E., GSK3beta isoform-selective regulation of depression, memory and hippocampal cell proliferation. Gene Brain Behav. 15 (2016), 348–355.
55. Post, R.M., Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am. J. Psychiatr. 149 (1992), 999–1010.
56. Rajkowska, G., Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol. Psychiatr. 48 (2000), 766–777.
57. Rajkowska, G., Miguel-Hidalgo, J.J., Wei, J., Dilley, G., Pittman, S.D., Meltzer, H.Y., Overholser, J.C., Roth, B.L., Stockmeier, C.A., Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol. Psychiatr. 45 (1999), 1085–1098.
58. Reich, C.G., Taylor, M.E., McCarthy, M.M., Differential effects of chronic unpredictable stress on hippocampal CB1 receptors in male and female rats. Behav. Brain Res. 203 (2009), 264–269.
59. Resstel, L.B., Joca, S.R., Moreira, F.A., Correa, F.M., Guimaraes, F.S., Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behav. Brain Res. 172 (2006), 294–298.
60. Revest, J.M., Dupret, D., Koehl, M., Funk-Reiter, C., Grosjean, N., Piazza, P.V., Abrous, D.N., Adult hippocampal neurogenesis is involved in anxiety-related behaviors. Mol. Psychiatr. 14:10 (2009), 959–967.
61. Rock, E.M., Bolognini, D., Limebeer, C.L., Cascio, M.G., Anavi-Goffer, S., Fletcher, P.J., Mechoulam, R., Pertwee, R.G., Parker, L.A., Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br. J. Pharmacol. 165 (2012), 2620–2634.
62. Rodgers, R.J., Evans, P.M., Murphy, A., Anxiogenic profile of AM-251, a selective cannabinoid CB1 receptor antagonist, in plus-maze-naive and plus-maze-experienced mice. Behav. Pharmacol. 16 (2005), 405–413.
63. Rossi, S., De Chiara, V., Musella, A., Sacchetti, L., Cantarella, C., Castelli, M., Cavasinni, F., Motta, C., Studer, V., Bernardi, G., Cravatt, B.F., Maccarrone, M., Usiello, A., Centonze, D., Preservation of striatal cannabinoid CB1 receptor function correlates with the antianxiety effects of fatty acid amide hydrolase inhibition. Mol. Pharmacol. 78 (2010), 260–268.
64. Rueda, D., Navarro, B., Martinez-Serrano, A., Guzman, M., Galve-Roperh, I., The endocannabinoid anandamide inhibits neuronal progenitor cell differentiation through attenuation of the Rap1/B-Raf/ERK pathway. J. Biol. Chem. 277 (2002), 46645–46650.
65. Russo, E.B., Burnett, A., Hall, B., Parker, K.K., Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem. Res. 30 (2005), 1037–1043.
66. Samuels, B.A., Hen, R., Neurogenesis and affective disorders. Eur. J. Neurosci. 33 (2011), 1152–1159.
67. Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., Belzung, C., Hen, R., Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301:5634 (2003), 805–809.
68. Schiavon, A.P., Bonato, J.M., Milani, H., Guimaraes, F.S., Weffort de Oliveira, R.M., Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice. Prog. Neuro-Psychopharmacol. Biol. Psychiatry 64 (2016), 27–34.
69. Silva, R., Mesquita, A.R., Bessa, J., Sousa, J.C., Sotiropoulos, I., Leao, P., Almeida, O.F., Sousa, N., Lithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: the role of glycogen-synthase-kinase-3beta. Neuroscience 152 (2008), 656–669.
70. Slopen, N., Williams, D.R., Fitzmaurice, G.M., Gilman, S.E., Sex, stressful life events, and adult onset depression and alcohol dependence: are men and women equally vulnerable?. Soc. Sci. Med. 73:4 (2011), 615–622.
71. Snyder, J.S., Soumier, A., Brewer, M., Pickel, J., Cameron, H.A., Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476 (2011), 458–461.
72. Soetanto, A., Wilson, R.S., Talbot, K., Un, A., Schneider, J.A., Sobiesk, M., Kelly, J., Leurgans, S., Bennett, D.A., Arnold, S.E., Association of anxiety and depression with microtubule-associated protein 2- and synaptopodin-immunolabeled dendrite and spine densities in hippocampal CA3 of older humans. Arch. Gen. Psychiatr. 67 (2010), 448–457.
73. Thomas, A., Baillie, G.L., Phillips, A.M., Razdan, R.K., Ross, R.A., Pertwee, R.G., Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br. J. Pharmacol. 150 (2007), 613–623.
74. Watanabe, K., Kayano, Y., Matsunaga, T., Yamamoto, I., Yoshimura, H., Inhibition of anandamide amidase activity in mouse brain microsomes by cannabinoids. Biol. Pharm. Bull. 19 (1996), 1109–1111.
75. Wolf, S.A., Bick-Sander, A., Fabel, K., Leal-Galicia, P., Tauber, S., Ramirez-Rodriguez, G., Muller, A., Melnik, A., Waltinger, T.P., Ullrich, O., Kempermann, G., Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun. Signal., 8(12), 2010.
76. Woolley, C.S., Gould, E., McEwen, B.S., Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res. 531 (1990), 225–231.