Cannabidiol injected into the bed nucleus of the stria terminalis reduces the expression of contextual fear conditioning via 5-HT 1A receptors

Journal of Psychopharmacology

Volumn 26, Issue 1, 2012, Pages 104-113

  Gomes, Felipe V ^a   Reis, Daniel G ^a   Alves, Fernando H F ^a   Corrêa, Fernando M A ^a   Guimarães, Francisco S ^a   Resstel, Leonardo B M ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Anxiolytics; autonomic responses; cannabinoids; conditioned emotional response; freezing

Indexed keywords

CANNABIDIOL; N [2 [4 (2 METHOXYPHENYL) 1 PIPERAZINYL]ETHYL] N (2 PYRIDYL)CYCLOHEXANECARBOXAMIDE; SEROTONIN 1A RECEPTOR;

ANIMAL TISSUE; ARTICLE; AVERSIVE BEHAVIOR; BED NUCLEUS; BRAIN NUCLEUS; CARDIOVASCULAR RESPONSE; CONTROLLED STUDY; FEAR; FREEZING; HEART RATE; MALE; MEAN ARTERIAL PRESSURE; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; STRIA TERMINALIS;

ANIMALS; BEHAVIOR, ANIMAL; CANNABIDIOL; CARDIOVASCULAR PHYSIOLOGICAL PHENOMENA; CONDITIONING (PSYCHOLOGY); FEAR; MALE; PIPERAZINES; PYRIDINES; RATS; RATS, WISTAR; RECEPTOR, SEROTONIN, 5-HT1A; SEPTAL NUCLEI; SEROTONIN 5-HT1 RECEPTOR ANTAGONISTS; SYNAPTIC TRANSMISSION;

EID: 84856432211     PISSN: 02698811     EISSN: 14617285     Source Type: Journal    
DOI: 10.1177/0269881110389095     Document Type: Article

References (89)

1. Akimova E, Lanzenberger R, Kasper S. The serotonin-1A receptor in anxiety disorders. Biol Psychiatry. 2009 ; 66: 627-635
2. Alheid GF. Extended amygdala and basal forebrain. Ann N Y Acad Sci. 2003 ; 985: 185-205 (Pubitemid 36521116)
3. Antoniadis EA, McDonald RJ. Discriminative fear conditioning to context expressed by multiple measures of fear in the rat. Behav Brain Res. 1999 ; 101: 1-13 (Pubitemid 29197205)
4. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999 ; 38: 1083-1152 (Pubitemid 29292403)
5. Beck CH, Fibiger HC. Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment. J Neurosci. 1995 ; 15: 709-720
6. Bisogno T, Hanus L, De Petrocellis L, Tchilibon S, Ponde DE, Brandi I, et al. 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. 2001 ; 134: 845-852 (Pubitemid 33016156)
7. Bitencourt RM, Pamplona FA, Takahashi RN. Facilitation of contextual fear memory extinction and anti-anxiogenic effects of AM404 and cannabidiol in conditioned rats. Eur Neuropsychopharmacol. 2008 ; 18: 849-859
8. Blanchard RJ, Blanchard DC. Crouching as an index of fear. J Comp Physiol Psychol. 1969 ; 67: 370-375
9. Campos AC, Guimarães FS. Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology (Berl). 2008 ; 199: 223-230
10. Carlini EA, Cunha JM. Hypnotic and antiepileptic effects of cannabidiol. J Clin Pharmacol. 1981 ; 21: 417S - 427S
11. Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A. 2006 ; 103: 7895-7900
12. Carrive P. Conditioned fear to environmental context: cardiovascular and behavioral components in the rat. Brain Res. 2000 ; 858: 440-445 (Pubitemid 30120009)
13. Casada JH, Dafny N. Restraint and stimulation of bed nucleus of the stria terminalis produce similar stress-like behaviors. Brain Res Bull. 1991 ; 27: 207-212
14. 1A binding in rat brain-a combined in situ hybridisation/in vitro receptor autoradiographic study. Brain Res. 1991 ; 561: 51-60
15. Commons KG, Connolley KR, Valentino RJ. A neurochemically distinct dorsal raphe-limbic circuit with a potential role in affective disorders. Neuropsychopharmacology. 2003 ; 28: 206-215
16. Cornea-Hébert V, Riad M, Wu C, Singh SK, Descarries L. Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat. J Comp Neurol. 1999 ; 409: 187-209 (Pubitemid 29264253)
17. Crestani CC, Alves FH, Tavares RF, Corrêa FM. Role of the bed nucleus of the stria terminalis in the cardiovascular responses to acute restraint stress in rats. Stress. 2009 ; 12: 268-278
18. Crippa JA, Zuardi AW, Garrido GE, Wichert-Ana L, Guarnieri R, Ferrari L, et al. Effects of cannabidiol (CBD) on regional cerebral blood flow. Neuropsychopharmacology. 2004 ; 29: 417-426 (Pubitemid 38175159)
19. Cunha JM, Carlini EA, Pereira AE, Ramos OL, Pimentel C, Gagliardi R, et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology. 1980 ; 21: 175-185 (Pubitemid 10039764)
20. Davis M, Walker DL, Lee Y. Amygdala and bed nucleus of the stria terminalis: differential roles in fear and anxiety measured with the acoustic startle reflex. Philos Trans R Soc Lond B Biol Sci. 1997a ; 352: 1675-1687 (Pubitemid 28000461)
21. Davis M, Walker DL, Lee Y. Roles of the amygdala and bed nucleus of the stria terminalis in fear and anxiety measured with the acoustic startle reflex. Possible relevance to PTSD. Ann N Y Acad Sci. 1997b ; 821: 305-331 (Pubitemid 27343031)
22. Davis M, Walker DL, Miles L, Grillon C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology. 2010 ; 35: 105-135
23. 1A and 5-HT2 receptors of the dorsal periaqueductal gray in the regulation of the defensive behaviors generated by the elevated T-maze. Brain Res Bull. 2004 ; 64: 181-188
24. Dong HW, Petrovich GD, Swanson LW. Topography of projections from amygdala to bed nuclei of the stria terminalis. Brain Res Brain Res Rev. 2001a ; 38: 192-246 (Pubitemid 34066502)
25. Dong HW, Petrovich GD, Watts AG, Swanson LW. Basic organization of projections from the oval and fusiform nuclei of the bed nuclei of the stria terminalis in adult rat brain. J Comp Neurol. 2001b ; 436: 430-455 (Pubitemid 32623063)
26. Dunn JD. Plasma corticosterone responses to electrical stimulation of the bed nucleus of the stria terminalis. Brain Res. 1987 ; 407: 327-331 (Pubitemid 17085791)
27. Dunn JD, Williams TJ. Cardiovascular responses to electrical stimulation of the bed nucleus of the stria terminalis. J Comp Neurol. 1995 ; 352: 227-234
28. Fadda P, Robinson L, Fratta W, Pertwee RG, Riedel G. Differential effects of THC- or CBD-rich cannabis extracts on working memory in rats. Neuropharmacology. 2004 ; 47: 1170-1179 (Pubitemid 39572708)
29. Fanselow MS. Conditioned and unconditional components of post-shock freezing. Pavlov J Biol Sci. 1980 ; 15: 177-182 (Pubitemid 11190893)
30. Fanselow MS. Contextual fear, gestalt memories, and the hippocampus. Behav Brain Res. 2000 ; 110: 73-81 (Pubitemid 30236293)
31. Fendt M, Fanselow MS. The neuroanatomical and neurochemical basis of conditioned fear. Neurosci Biobehav Rev. 1999 ; 23: 743-760 (Pubitemid 29282023)
32. Frank LM, Stanley GB, Brown EN. Hippocampal plasticity across multiple days of exposure to novel environments. J Neurosci. 2004 ; 24: 7681-7689 (Pubitemid 39186823)
33. Fusar-Poli P, Crippa JA, Bhattacharyya S, Borgwardt SJ, Allen P, Martin-Santos R, et al. Distinct effects of delta 9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009 ; 66: 95-105
34. Gray TS, Piechowski RA, Yracheta JM, Rittenhouse PA, Bethea CL, Van de Kar LD. Ibotenic acid lesions in the bed nucleus of the stria terminalis attenuate conditioned stress-induced increases in prolactin, ACTH and corticosterone. Neuroendocrinology. 1993 ; 57: 517-524 (Pubitemid 23170158)
35. Guimarães FS, Chiaretti TM, Graeff FG, Zuardi AW. Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology (Berl). 1990 ; 100: 558-559 (Pubitemid 20102368)
36. Guo JD, Hammack SE, Hazra R, Levita L, Rainnie DG. Bi-directional modulation of bed nucleus of stria terminalis neurons by 5-HT: molecular expression and functional properties of excitatory 5-HT receptor subtypes. Neuroscience. 2009 ; 164: 1776-1793
37. Hammack SE, Guo JD, Hazra R, Dabrowska J, Myers KM, Rainnie DG. The response of neurons in the bed nucleus of the stria terminalis to serotonin: implications for anxiety. Prog Neuropsychopharmacol Biol Psychiatry. 2009 ; 33: 1309-1320
38. Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Delta 9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A. 1998 ; 95: 8268-8273 (Pubitemid 28326102)
39. Heidmann DE, Szot P, Kohen R, Hamblin MW. Function and distribution of three rat 5-hydroxytryptamine7 (5-HT7) receptor isoforms produced by alternative splicing. Neuropharmacology. 1998 ; 37: 1621-1632
40. 1A receptor mutant mice. Proc Natl Acad Sci U S A. 1998 ; 95: 15049-15054 (Pubitemid 29003754)
41. Herman JP, Cullinan WE. Neurocircuitry of stress: central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neurosci. 1997 ; 20: 78-84 (Pubitemid 27050702)
42. Herman JP, Cullinan WE, Watson SJ. Involvement of the bed nucleus of the stria terminalis in tonic regulation of paraventricular hypothalamic CRH and AVP mRNA expression. J Neuroendocrinol. 1994 ; 6: 433-442 (Pubitemid 24254243)
43. Iuvone T, Esposito G, De Filippis D, Scuderi C, Steardo L. Cannabidiol: a promising drug for neurodegenerative disorders?. CNS Neurosci Ther. 2009 ; 15: 65-75
44. Izzo AA, Borrelli F, Capasso R, Di Marzo V, Mechoulam R. Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Trends Pharmacol Sci. 2009 ; 30: 515-527
45. Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlini EA. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man. Eur J Pharmacol. 1974 ; 28: 172-177
46. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E. Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol. 2006 ; 372: 354-361
47. Kia HK, Miquel MC, Brisorgueil MJ, Daval G, Riad M, El Mestikawy S, et al. Immunocytochemical localization of serotonin1A receptors in the rat central nervous system. J Comp Neurol. 1996 ; 365: 289-305
48. Lemos JI, Resstel LB, Guimarães FS. Involvement of the prelimbic prefrontal cortex on cannabidiol-induced attenuation of contextual conditioned fear in rats. Behav Brain Res. 2010 ; 207: 105-111
49. Levita L, Hammack SE, Mania I, Li XY, Davis M, Rainnie DG. 5-hydroxytryptamine1A-like receptor activation in the bed nucleus of the stria terminalis: electrophysiological and behavioral studies. Neuroscience. 2004 ; 128: 583-596 (Pubitemid 39277428)
50. Lowry CA, Hale MW, Evans AK, Heerkens J, Staub DR, Gasser PJ, et al. Serotonergic systems, anxiety, and affective disorder: focus on the dorsomedial part of the dorsal raphe nucleus. Ann N Y Acad Sci. 2008 ; 1148: 86-94
51. 1A receptor activation. Br J Pharmacol. 2010 ; 159: 950-957
52. Massi L, Elezgarai I, Puente N, Reguero L, Grandes P, Manzoni OJ, et al. Cannabinoid receptors in the bed nucleus of the stria terminalis control cortical excitation of midbrain dopamine cells in vivo. J Neurosci. 2008 ; 28: 10496-10508
53. McQueen DS, Bond SM, Smith PJ, Balali-Mood K, Smart D. Cannabidiol lacks the vanilloid VR1-mediated vasorespiratory effects of capsaicin and anandamide in anaesthetised rats. Eur J Pharmacol. 2004 ; 491: 181-189 (Pubitemid 38609476)
54. Mengod G, Nguyen H, Le H, Waeber C, Lübbert H, Palacios JM. The distribution and cellular localization of the serotonin 1C receptor mRNA in the rodent brain examined by in situ hybridization histochemistry. Comparison with receptor binding distribution. Neuroscience. 1990 ; 35: 577-591 (Pubitemid 20198391)
55. Milad MR, Quirk GJ. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. 2002 ; 420: 70-74 (Pubitemid 35291441)
56. Moreira FA, Aguiar DC, Guimarães FS. Anxiolytic-like effect of cannabidiol in the rat Vogel conflict test. Prog Neuropsychopharmacol Biol Psychiatry. 2006 ; 30: 1466-1471 (Pubitemid 44634958)
57. Onaivi ES, Green MR, Martin BR. Pharmacological characterization of cannabinoids in the elevated plus maze. J Pharmacol Exp Ther. 1990 ; 253: 1002-1009 (Pubitemid 20209356)
58. Parks CL, Robinson PS, Sibille E, Shenk T, Toth M. Increased anxiety of mice lacking the serotonin1A receptor. Proc Natl Acad Sci U S A. 1998 ; 95: 10734-10739
59. Paxinos G, Watson C The rat brain in stereotaxic coordinates. 1997 ) The rat brain in stereotaxic coordinates, 2nd ed.Sydney: Academic Press. Sydney: Academic Press ; 1997 :
60. Petitet F, Jeantaud B, Reibaud M, Imperato A, Dubroeucq MC. Complex pharmacology of natural cannabinoids: evidence for partial agonist activity of delta 9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Life Sci. 1998 ; 63: PL1-6
61. Phelix CF, Liposits Z, Paull WK. Serotonin-CRF interaction in the bed nucleus of the stria terminalis: a light microscopic double-label immunocytochemical analysis. Brain Res Bull. 1992 ; 28: 943-948
62. Pompeiano M, Palacios JM, Mengod G. Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors. Brain Res Mol Brain Res. 1994 ; 23: 163-178
63. Rainnie DG. Neurons of the bed nucleus of the stria terminalis (BNST). Electrophysiological properties and their response to serotonin. Ann N Y Acad Sci. 1999 ; 877: 695-699 (Pubitemid 29351894)
64. Ramboz S, Oosting R, Amara DA, Kung HF, Blier P, Mendelsohn M, et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc Natl Acad Sci U S A. 1998 ; 95: 14476-14481 (Pubitemid 28549392)
65. Resstel LB, Alves FH, Reis DG, Crestani CC, Corrêa FM, Guimarães FS. Anxiolytic-like effects induced by acute reversible inactivation of the bed nucleus of stria terminalis. Neuroscience. 2008 ; 154: 869-876
66. Resstel LB, Joca SR, Guimarães FG, Corrêa FM. Involvement of medial prefrontal cortex neurons in behavioral and cardiovascular responses to contextual fear conditioning. Neuroscience. 2006a ; 143: 377-385 (Pubitemid 44716591)
67. Resstel LB, Joca SR, Moreira FA, Corrêa FM, Guimarães FS. Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats. Behav Brain Res. 2006b ; 172: 294-298 (Pubitemid 44148829)
68. 1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009 ; 156: 181-188
69. Rickels K, Rynn M. Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry. 2002 ; 63 (Suppl 14). 9-16 (Pubitemid 36008862)
70. Rudy JW, Huff NC, Matus-Amat P. Understanding contextual fear conditioning: insights from a two-process model. Neurosci Biobehav Rev. 2004 ; 28: 675-685 (Pubitemid 39535865)
71. Russo EB, Burnett A, Hall B, Parker KK. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochem Res. 2005 ; 30: 1037-1043 (Pubitemid 41570039)
72. Sullivan GM, Apergis J, Bush DE, Johnson LR, Hou M, Ledoux JE. Lesions in the bed nucleus of the stria terminalis disrupt corticosterone and freezing responses elicited by a contextual but not by a specific cue-conditioned fear stimulus. Neuroscience. 2004 ; 128: 7-14 (Pubitemid 39140675)
73. Thomas BF, Gilliam AF, Burch DF, Roche MJ, Seltzman HH. Comparative receptor binding analyses of cannabinoid agonists and antagonists. J Pharmacol Exp Ther. 1998 ; 285: 285-292 (Pubitemid 28207598)
74. To ZP, Bonhaus DW, Eglen RM, Jakeman LB. Characterization and distribution of putative 5-HT7 receptors in guinea-pig brain. Br J Pharmacol. 1995 ; 115: 107-116
75. 1A subtype. Eur J Pharmacol. 1985 ; 113: 463-464 (Pubitemid 16249855)
76. Vertes RP. Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience. 2006 ; 142: 1-20 (Pubitemid 44353937)
77. Waeber C, Moskowitz MA. [3H] sumatriptan labels both 5-HT1D and 5-HT1F receptor binding sites in the guinea pig brain: an autoradiographic study. Naunyn Schmiedebergs Arch Pharmacol. 1995 ; 352: 263-275
78. Waeber C, Sebben M, Nieoullon A, Bockaert J, Dumuis A. Regional distribution and ontogeny of 5-HT4 binding sites in rodent brain. Neuropharmacology. 1994 ; 33: 527-541 (Pubitemid 24168725)
79. Walker DL, Davis M. Double dissociation between the involvement of the bed nucleus of the stria terminalis and the central nucleus of the amygdala in startle increases produced by conditioned versus unconditioned fear. J Neurosci. 1997 ; 17: 9375-9383 (Pubitemid 27498464)
80. Walker DL, Toufexis DJ, Davis M. Role of the bed nucleus of the stria terminalis versus the amygdala in fear, stress, and anxiety. Eur J Pharmacol. 2003 ; 463: 199-216 (Pubitemid 36205081)
81. Wright DE, Seroogy KB, Lundgren KH, Davis BM, Jennes L. Comparative localization of serotonin1A, 1C, and 2 receptor subtype mRNAs in rat brain. J Comp Neurol. 1995 ; 351: 357-373
82. Xu T, Pandey SC. Cellular localization of serotonin(2A) (5HT(2A)) receptors in the rat brain. Brain Res Bull. 2000 ; 51: 499-505 (Pubitemid 30176094)
83. Yang KH, Galadari S, Isaev D, Petroianu G, Shippenberg TS, Oz M. The nonpsychoactive cannabinoid cannabidiol inhibits 5-hydroxytryptamine3A receptor-mediated currents in Xenopus laevis oocytes. J Pharmacol Exp Ther. 2010 ; 333: 547-554 (Pubitemid 350005116)
84. 1A receptors. Br J Pharmacol. 2010 ; 159: 122-128
85. Zhang WN, Murphy CA, Feldon J. Behavioural and cardiovascular responses during latent inhibition of conditioned fear: measurement by telemetry and conditioned freezing. Behav Brain Res. 2004 ; 154: 199-209 (Pubitemid 39070468)
86. Zuardi AW. Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr. 2008 ; 30: 271-280
87. Zuardi AW, Cosme RA, Graeff FG, Guimarães FS. Effects of ipsapirone and cannabidiol on human experimental anxiety. J Psychopharmacol. 1993 ; 7 (Suppl 1). 82-88 (Pubitemid 23099702)
88. Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimarães FS. Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res. 2006 ; 39: 421-429
89. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl). 1982 ; 76: 245-250 (Pubitemid 12129400)