Cannabidiol-induced panicolytic-like effects and fear-induced antinociception impairment: the role of the CB1 receptor in the ventromedial hypothalamus

  • Asmat Ullah Khan
  • Luiz Luciano Falconi-Sobrinho
  • Tayllon dos Anjos-Garcia
  • Maria de Fátima dos Santos Sampaio
  • José Alexandre de Souza Crippa
  • Leda Menescal-de-Oliveira
  • Norberto Cysne CoimbraEmail author
Original Investigation



The behavioural effects elicited by chemical constituents of Cannabis sativa, such as cannabidiol (CBD), on the ventromedial hypothalamus (VMH) are not well understood. There is evidence that VMH neurons play a relevant role in the modulation of unconditioned fear-related defensive behavioural reactions displayed by laboratory animals.


This study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and to investigate the role played by this cannabinoid receptor in the effect of CBD on the control of defensive behaviours and unconditioned fear-induced antinociception.


A panic attack-like state was triggered in Wistar rats by intra-VMH microinjections of N-methyl-d-aspartate (NMDA). One of three different doses of CBD was microinjected into the VMH prior to local administration of NMDA. In addition, the most effective dose of CBD was used after pre-treatment with the CB1 receptor selective antagonist AM251, followed by NMDA microinjections in the VMH.


The morphological procedures demonstrated distribution of labelled CB1 receptors on neuronal perikarya situated in dorsomedial, central and ventrolateral divisions of the VMH. The neuropharmacological approaches showed that both panic attack-like behaviours and unconditioned fear-induced antinociception decreased after intra-hypothalamic microinjections of CBD at the highest dose (100 nmol). These effects, however, were blocked by the administration of the CB1 receptor antagonist AM251 (100 pmol) in the VMH.


These findings suggest that CBD causes panicolytic-like effects and reduces unconditioned fear-induced antinociception when administered in the VMH, and these effects are mediated by the CB1 receptor-endocannabinoid signalling mechanism in VMH.


Cannabidiol CB1 receptor Panic attack-like behaviour Endocannabinoid system Unconditioned fear-induced antinociception Ventromedial hypothalamus 



The authors thank Daoud Hibrahim Elias-Filho for his expert technical assistance.

Authors’ contributions

A. U. Khan performed the experiments and wrote the manuscript. L. L. Falconi-Sobrinho and T. dos Anjos-Garcia wrote the manuscript, analysed and interpreted the data, revised figures and performed morphometry. N.C. Coimbra designed the experiments, the enriched polygonal arena, analysed and interpreted the data, wrote the manuscript and approved the final manuscript. M. de F. dos Santos Sampaio performed morphometry. L. Menescal-de-Oliveira interpreted the data and J.A.S. Crippa analysed and interpreted the data. All authors have approved the final version of the manuscript. We are entirely responsible for the scientific content of this paper.

Funding information

This research was supported by FAPESP (Research grants 2007/01174-1 and 2012/03798-0 and 2017/11855-8) and CNPq (Research grants 483763/2010-1, 474853/2013-6 and 427397/2018-9). A. U. Khan was supported by The World Academy of Sciences for the Advancement of Science in Developing Countries (TWAS)-CNPq (Scientiae Doctor Fellowship CNPq grant 1902229/2014-4). L.L. Falconi-Sobrinho was supported by FAPESP (Magister Scientiae grant 2013/ 10984-8) and CNPq (M.Sc. fellowship grant 134267/2013-3; Sc. D. fellowship grant 145258/2015-7). T. dos Anjos-Garcia was financially supported by CNPq (M.Sc. fellowship, process 130124/2012-5; Sc. D. fellowship, process 141124/2014-8) and is a postdoctoral researcher supported by FAPESP (grant 2017/22647-7). M. de Fátima dos Santos Sampaio is a postdoctoral researcher supported by CNPq (PDJ grant 155489/2018-6). N.C. Coimbra is a researcher (level 1A) at CNPq (Science Productivity grants 301905/2010-0 and 301341/215-0). D.H. Elias-Filho is supported by CNPq (grant 372877/2010-9).

Compliance with ethical standards

All experimental trials complied with the Ethical Commission in Animal Experimentation of the FMRP-USP, which fulfils the principles of ethics for animal research adopted by the National Council for Control of Animal Experimentation (CONCEA) and were approved by the Commission of Ethics in Animal Research (CEUA-FMRP-USP) (process 107/2012).

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

213_2019_5435_MOESM1_ESM.pdf (321 kb)
ESM 1 (PDF 320 kb)


  1. Aimone LD, Bauer CA, Gebhart GF (1988) Brain-stem relays mediating stimulation-produced antinociception from the lateral hypothalamus in the rat. J Neurosci 8:2652–2663PubMedPubMedCentralCrossRefGoogle Scholar
  2. Almada RC, Coimbra NC (2015) Recruitment of striatonigral disinhibitory and nigrotectal inhibitory GABAergic pathways during the organization of defensive behavior by mice in a dangerous environment with the venomous snake Bothrops alternatus (Reptilia Viperidae). Synapse 69:299–313PubMedCrossRefGoogle Scholar
  3. Almada RC, Roncon CM, Elias-Filho DH, Coimbra NC (2015) Endocannabinoid signaling mechanisms in the substantia nigra pars reticulata modulate GABAergic nigrotectal pathways in mice threatened by urutu-cruzeiro venomous pit viper. Neuroscience 303:503–514PubMedCrossRefGoogle Scholar
  4. Azad SC, Eder M, Marsicano G, Lutz B, Zieglgänsberger W, Rammes G (2003) Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse. Learn Mem 10:116–128PubMedPubMedCentralCrossRefGoogle Scholar
  5. Azad SC, Kurz J, Marsicano G, Lutz B, Zieglgänsberger W, Rammes G (2008) Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in the lateral amygdala. Learn Mem 15:143–152PubMedPubMedCentralCrossRefGoogle Scholar
  6. Battista N, Di Tommaso M, Bari M, Maccarrone M (2012) The endocannabinoid system: an overview. Front Behav Neurosci 6:9PubMedPubMedCentralCrossRefGoogle Scholar
  7. Biagioni AF, Freitas RL, de Silva JA, de Oliveira RC, de Oliveira R, de Alves VM, Coimbra NC (2013) Serotonergic neural links from the dorsal raphe nucleus modulate defensive behaviours organised by the dorsomedial hypothalamus and the elaboration of fear-induced antinociception via locus coeruleus pathways. Neuropharmacology 67:379–394PubMedCrossRefGoogle Scholar
  8. Biagioni AF, dos Anjos-Garcia T, Ullah F, Fisher IR, Falconi-Sobrinho LL, de Freitas RL, Felippotti TT, Coimbra NC (2016a) Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test. Behav Brain Res 298(Pt B):65–77PubMedCrossRefGoogle Scholar
  9. Biagioni AF, Oliveira RC, de Oliveira R, da Silva JA, dos Anjos-Garcia T, Roncon CM, Corrado AP, Zangrossi H Jr (2016b) 5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception. Eur Neuropsychopharmacol 26:532–545PubMedCrossRefGoogle Scholar
  10. Bisogno T, Hanus L, de Petrocellis L, Tchjlibon S, Ponde DE, Brandi I, Moriello AS, Davis JB, Mechoulam R, Di Marzo V (2001) 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 134:845–852PubMedPubMedCentralCrossRefGoogle Scholar
  11. Blessing EM, Steenkamp MM, Manzanares J, Marmar CR (2015) Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics 12:825–836PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bolles RC, Fanselow MS (1980) A perceptual-defensive-recuperative model of fear and pain. Behav Brain Sci 3:291CrossRefGoogle Scholar
  13. Bushnell MC, Čeko M, Low LA (2013) Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci 14:502–511PubMedPubMedCentralCrossRefGoogle Scholar
  14. Butler RK, Finn DP (2009) Stress-induced analgesia. Prog Neurobiol 88:184–202PubMedCrossRefGoogle Scholar
  15. Calvo F, Almada RC, dos Anjos-Garcia T, Falconi-Sobrinho LL, Paschoalin-Maurin T, Bazaglia-de-Sousa G, Lobão-Soares B, Coimbra NC (2019a) Panicolytic-like effect of μ1-opioid receptor blockade into the inferior colliculus of rats threatened by Crotalus durissus terrificus pit vipers. J Psychoharmacol 33(5):577–588CrossRefGoogle Scholar
  16. Calvo F, Lobão-Soares B, de Freitas RL, Paschoalin-Maurin T, dos Anjos-Garcia T, Medeiros P, da Silva JA, Lovick TA, Coimbra NC (2019b) The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade. J Psychopharmacol 33(1):51–61PubMedCrossRefGoogle Scholar
  17. Canteras NS (2002) The medial hypothalamic defensive system: hodological organization and functional implications. Pharmacol Biochem Behav 71:481–491PubMedCrossRefGoogle Scholar
  18. Campos AC, Guimarães FS (2008) Involvement of 5HT1A receptors in the anxiolytic-like effects of cannabidiol injected into the dorsolateral periaqueductal gray of rats. Psychopharmacology 199:223–230PubMedCrossRefGoogle Scholar
  19. Casarotto PC, Terzian ALB, Aguiar DC, Zangrossi H, Guimarães FS, Wotjak CT, Moreira FA (2012) Opposing roles for cannabinoid receptor type-1 (CB1) and transient receptor potential vanilloid type-1 channel (TRPV1) on the modulation of panic-like responses in rats. Neuropsychopharmacology 37:478–486PubMedCrossRefGoogle Scholar
  20. Coimbra NC, Calvo F, Almada RC, Freitas RL, Paschoalin-Maurin T, dos Anjos-Garcia T, Elias-Filho DH, Ubiali WA, Lobão-Soares B, Tracey I (2017a) Opioid neurotransmission modulates defensive behavior and fear-induced antinociception in dangerous environments. Neuroscience 354:178–195PubMedCrossRefGoogle Scholar
  21. Coimbra NC, de Oliveira R, Freitas RL, Ribeiro SJ, Borelli KG, Pacagnella RC, Moreira JE, da Silva LA, Mello LL, Lunardi LO, Brandão ML (2006) Neuroanatomical approaches of the tectum-reticular pathways and immunohistochemical evidence for serotonin-positive perikarya on neuronal substrates of the superior colliculus and periaqueductal gray matter involved in the elaboration of the defensive behavior and fear-induced analgesia. Exp Neurol 197:93–112PubMedCrossRefGoogle Scholar
  22. Coimbra NC, Mendes-Gomes J, da Silva JA, dos Anjos-Garcia T, Ullah F, Almada R.C (2017b) Ethological and morphological perspectives for the investigation of panicolytic-like effect of cannabidiol. In: The handbook of cannabis and related pathologies: biology, diagnosis, treatment, and pharmacology (Victor R. Preedy, ed.). Elsevier Science Publishers Amsterdam pp. e140-e149Google Scholar
  23. Coimbra NC, Paschoalin-Maurin T, Bassi GS, Kanashiro A, Biagioni AF, Felippotti TT, Elias-Filho DH, Mendes-Gomes J, Cysne-Coimbra JP, Almada RC, Lobão-Soares B (2017c) Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests. Braz J Psychiatr 39:72–83CrossRefGoogle Scholar
  24. Connell K, Bolton N, Olsen D, Piomelli D, Hohmann AG (2006) Role of the basolateral nucleus of the amygdala in endocannabinoid-mediated stress-induced analgesia. Neurosci Lett 397:180–184PubMedCrossRefGoogle Scholar
  25. da Silva JA, Biagioni AF, Almada RC, de Souza Crippa JA,  Hallak JEC, Zuardi AW, Coimbra NC (2015) Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: the role of CB1-cannabinoid receptor in the ventral mesencephalon. Eur J Pharmacol 758:153–163Google Scholar
  26. da Silva Soares R Jr, Falconi-Sobrinho LL, dos Anjos-Garcia T, Coimbra NC (2019) 5-Hydroxytryptamine 2A receptors of the dorsal raphe nucleus modulate panic-like behaviours and mediate fear-induced antinociception elicited by neuronal activation in the central nucleus of the inferior colliculus. Behav Brain Res 357-358:71–81PubMedCrossRefGoogle Scholar
  27. de Gregorio D, McLaughlin RJ, Posa L, Ochoa-Sanchez R, EnnsJ L-CM, Aboud M, Maione S, Comai S, Gobbi G (2019) Cannabidiol modulates serotonergic transmission and reverses both allodynia and anxiety-like behavior in a model of neuropathic pain. Pain 160:136–150PubMedCrossRefGoogle Scholar
  28. dos Anjos-Garcia T, Ullah F, Falconi-Sobrinho LL, Coimbra NC (2017) CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABAA receptor blockade in the dorsomedial division of the ventromedial hypothalamus. Neuropharmacology 113:156–166PubMedCrossRefGoogle Scholar
  29. Falconi-Sobrinho LL, dos Anjos-Garcia T, Elias-Filho DH, Coimbra NC (2017a) Unravelling cortico-hypothalamic pathways regulating unconditioned fear-induced antinociception and defensive behaviours. Neuropharmacology 113:367–385PubMedCrossRefGoogle Scholar
  30. Falconi-Sobrinho LL, dos Anjos-Garcia T, de Oliveira R, Coimbra NC (2017b) Decrease in NMDA receptor-signalling activity in the anterior cingulate cortex diminishes defensive behaviour and unconditioned fear-induced antinociception elicited by GABAergic tonic inhibition impairment in the posterior hypothalamus. Eur Neuropsychopharmacol 27:1120–1131PubMedCrossRefGoogle Scholar
  31. Falconi-Sobrinho LL, Coimbra NC (2018) The nitric oxide donor SIN-1-produced panic-like behaviour and fear-induced antinociception are modulated by NMDA receptors in the anterior hypothalamus. J Psychopharmacol 32:711–722PubMedCrossRefGoogle Scholar
  32. Freitas RL, Uribe-Mariño A, Castiblanco-Urbina MA, Elias-Filho DH, Coimbra NC (2009) GABAA receptor blockade in dorsomedial and ventromedial nuclei of the hypothalamus evokes panic-like elaborated defensive behaviour followed by innate fear-induced antinociception. Brain Res 1305:118–131PubMedCrossRefGoogle Scholar
  33. Glass M, Dragunow M, Faull RL (1997) Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77:299–318PubMedCrossRefGoogle Scholar
  34. Gomes FV, Resstel LBM, Guimarães FS (2011) The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology 213:465–473PubMedCrossRefGoogle Scholar
  35. Gonçalves TCT, Londe AK, Albano RIP, de Araújo Júnior AT, de Aguiar AM, Biagioni AF, Vasconcellos THF, dos Reis Ferreira CM, Teixeira DG, de Souza Crippa JA, Vieira D, Coimbra NC (2014) Cannabidiol and endogenous opioid peptide-mediated mechanisms modulate antinociception induced by transcutaneous electrostimulation of the peripheral nervous system. J Neurol Sci 347:82–89PubMedCrossRefGoogle Scholar
  36. Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker FM, Holmes FV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) An endocannabinoid mechanism for stress-induced analgesia. Nature 435:1108–1112PubMedCrossRefGoogle Scholar
  37. Iannotti FA, Hill CL, Leo A, Alhusaini A, Soubrane C, Mazzarella E, Russo E, Whalley BJ, Di Marzo V, Stephens GJ (2014) Nonpsychotropic plant cannabinoids, cannabidivarin (CBDV) and cannabidiol (CBD), activate and desensitize transient receptor potential vanilloid 1 (TRPV1) channels in vitro: potential for the treatment of neuronal hyperexcitability. ACS Chem Neurosci 5:1131–1141PubMedCrossRefGoogle Scholar
  38. Johnson PL, Shekhar A (2006) Panic-prone state induced in rats with GABA dysfunction in the dorsomedial hypothalamus is mediated by NMDA receptors. J Neurosci 26:7093–7104PubMedPubMedCentralCrossRefGoogle Scholar
  39. López-Moreno JA, González-Cuevas G, Moreno G, Navarro M (2008) The pharmacology of the endocannabinoid system: functional and structural interactions with other neurotransmitter systems and their repercussions in behavioral addiction. Addict Biol 13:160–187PubMedCrossRefGoogle Scholar
  40. Mackie K (2008) Cannabinoid receptors: where they are and what they do. J Neuroendocrinol 20:10–14PubMedCrossRefGoogle Scholar
  41. Marinho ALZ, Vila-Verde C, Fogaça MV, Guimarães FS (2015) Effects of intra-infralimbic prefrontal cortex injections of cannabidiol in the modulation of emotional behaviors in rats: contribution of 5HT1A receptors and stressful experiences. Behav Brain Res 286:49–56PubMedCrossRefGoogle Scholar
  42. Mechoulam R, Peters M, Murillo-Rodrigue E, Hanuš LO (2007) Cannabidiol – recent advances. Chem Biodivers 4:1678–1692PubMedCrossRefGoogle Scholar
  43. Maione S, Piscitelli F, Gatta L, Vita D, De Petrocellis L, Palazzo E, de Novellis V, Di Marzo V (2011) Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. Br J Pharmacol 162:584–596PubMedPubMedCentralCrossRefGoogle Scholar
  44. McPartland JM, Duncan M, Di Marzo V, Pertwee RG (2015) Are cannabidiol and Δ(9)-tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol 172:737–753PubMedPubMedCentralCrossRefGoogle Scholar
  45. Misner DL, Sullivan JM (1999) Mechanism of cannabinoid effects on long-term potentiation and depression in hippocampal CA1 neurons. J Neurosci 19:6795–6805PubMedPubMedCentralCrossRefGoogle Scholar
  46. Millan MJ (2002) Descending control of pain. Prog Neurobiol 66:355–474PubMedCrossRefGoogle Scholar
  47. Myers RD (1966) Injection of solutions into cerebral tissue: relation between volume and diffusion. Physiol Behav 1:171–174CrossRefGoogle Scholar
  48. Neelakantan H, Tallarida RJ, Reichenbach ZW, Tuma RF, Ward SJ, Walker EA (2015) Distinct interactions of cannabidiol and morphine in three nociceptive behavioral models in mice. Behav Pharmacol 26:304–314PubMedCrossRefGoogle Scholar
  49. Palazzo E, de Novellis V, Marabese I, Cuomo D, Rossi F, Berrino L, Rossi F, Maione S (2002) Interaction between vanilloid and glutamate receptors in the central modulation of nociception. Eur J Pharmacol 439:69–75PubMedCrossRefGoogle Scholar
  50. Paschoalin-Maurin T, dos Anjos-Garcia T, Falconi-Sobrinho LL, de Freitas RL, Coimbra JPC, Laure CJ, Coimbra NC (2018) The rodent-versus-wild snake paradigm as a model for studying anxiety- and panic-like behaviors: face, construct and predictive validities. Neuroscience 369:336–349PubMedCrossRefGoogle Scholar
  51. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, San DiegoGoogle Scholar
  52. Roche M, O’Connor E, Diskin C, Finn DP (2007) The effect of CB(1) receptor antagonism in the right basolateral amygdala on conditioned fear and associated analgesia in rats. Eur J Neurosci 26:2643–2653PubMedCrossRefGoogle Scholar
  53. Rodríguez-Muñoz M, Onetti Y1, Cortés-Montero E, Garzón J, Sánchez-Blázquez P (2018) Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor. Mol Brain 17:11–51Google Scholar
  54. Routtenberg A (1972) Memory as input-output reciprocity: an integrative neurobiological theory. Ann N Y Acad Sci 193:159–174PubMedCrossRefGoogle Scholar
  55. Russo EB, Burnett A, Hall B, Parker KK (2005) Agonist properties of cannabidiol at 5-HT1A receptors. Neurochem Res 30:1037–1043PubMedCrossRefGoogle Scholar
  56. Schier ARM, Ribeiro NP, Silva AC, Hallak JEC, Crippa JAS, Nardi AE, Zuardi AW (2012) Cannabidiol, a Cannabis sativa constituent, as an anxiolytic drug. Rev Bras Psiquiatr 34:S104–S117PubMedCrossRefGoogle Scholar
  57. Shekhar A, DiMicco JA (1987) Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats. Neuropharmacology 26:407–417PubMedCrossRefGoogle Scholar
  58. Soares VP, Campos AC, Bortoli VC, Zangrossi H Jr, Guimarães FS, Zuardi AW (2010) Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors. Behav Brain Res 213:225–229CrossRefGoogle Scholar
  59. Spiacci A Jr, de Oliveira ST, da Silva GSF, Glass ML, Schenberg LC, Garcia-Cairasco N, Zangrossi H Jr (2015) Serotonin in the dorsal periaqueductal gray inhibits panic-like defensive behaviors in rats exposed to acute hypoxia. Neuroscience 307:191–198PubMedCrossRefGoogle Scholar
  60. Spiacci A Jr, Vilela-Costa HH, Sant'Ana AB, Fernandes GG, Frias AT, da Silva GSF, Antunes-Rodrigues J, Zangrossi H Jr (2018) Panic-like escape response elicited in mice by exposure to CO2, but not hypoxia. Prog Neuro-Psychopharmacol Biol Psychiatry 81:178–186CrossRefGoogle Scholar
  61. Takahashi KA, Castillo PE (2006) The CB1 cannabinoid receptor mediates glutamatergic synaptic suppression in the hippocampus. Neuroscience 139:795–802PubMedCrossRefGoogle Scholar
  62. Twardowschy A, Castiblanco-Urbina MA, Uribe-Mariño A, Biagioni AF, Salgado-Rohner CJ, de Souza-Crippa JA, Coimbra NC (2013) The role of 5-HT1A receptors in the anti-aversive effects of cannabidiol on panic attack-like behaviors evoked in the presence of the wild snake Epicrates cenchria crassus (Reptilia, Boidae). J Psychopharmacol 27:1149–1159PubMedCrossRefGoogle Scholar
  63. Ullah F, dos Anjos-Garcia T, Mendes-Gomes J, Elias-Filho DH, Falconi-Sobrinho LL, de Freitas RL, Khan AU, de Oliveira R, Coimbra NC (2017) Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour. Behav Brain Res 319:135–147PubMedCrossRefGoogle Scholar
  64. Ullah F, dos Anjos-Garcia T, dos Santos IR, Biagioni AF, Coimbra NC (2015) Relevance of dorsomedial hypothalamus, dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal gray matter in the organization of freezing or oriented and non-oriented escape emotional behaviors. Behav Brain Res 293:143–152PubMedCrossRefGoogle Scholar
  65. Uribe-Mariño A, Francisco A, Castiblanco-Urbina MA, Twardowschy A, Salgado-Rohner CJ, Crippa JAS, Hallak JEC, Zuardi AW, Coimbra NC (2012) Anti-aversive effects of cannabidiol on innate fear-induced behaviors evoked by an ethological model of panic attacks based on a prey vs the wild snake Epicrates cenchria crassus confrontation paradigm. Neuropsychopharmacology 37:412–421PubMedCrossRefGoogle Scholar
  66. Viana TG, Hott SC, Resstel LB, Aguiar DC, Moreira FA (2015) Anti-aversive role of the endocannabinoid system in the periaqueductal gray stimulation model of panic attacks in rats. Psychopharmacology 232:1545–1553PubMedCrossRefGoogle Scholar
  67. Wilent WB, Oh MY, Buetefisch CM, Bailes JE, Cantella D, Angle C, Whiting DM (2010) Induction of panic attack by stimulation of the ventromedial hypothalamus. J Neurosurg 112:1295–1298PubMedCrossRefGoogle Scholar
  68. Wolkers CPB, Barbosa Junior A, Menescal-de-Oliveira L, Hoffmann A (2015) Acute administration of a cannabinoid CB1 receptor antagonist impairs stress-induced antinociception in fish. Physiol Behav 142:37–41PubMedCrossRefGoogle Scholar
  69. Zou S, Somvanshi RK, Paik S, Kumar U (2015) Colocalization of cannabinoid receptor 1 with somatostatin and neuronal nitric oxide synthase in rat brain hypothalamus. J Mol Neurosci 55:480–491PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Asmat Ullah Khan
    • 1
    • 2
    • 3
  • Luiz Luciano Falconi-Sobrinho
    • 1
    • 3
    • 4
  • Tayllon dos Anjos-Garcia
    • 1
    • 3
  • Maria de Fátima dos Santos Sampaio
    • 1
  • José Alexandre de Souza Crippa
    • 5
  • Leda Menescal-de-Oliveira
    • 3
    • 6
  • Norberto Cysne Coimbra
    • 1
    • 3
    • 4
    Email author
  1. 1.Laboratory of Neuroanatomy and Neuropsychobiology, Department of PharmacologyRibeirão Preto Medical School of the University of São Paulo (FMRP-USP)São PauloBrazil
  2. 2.Department of Eastern Medicine and Surgery, School of Medical and Health SciencesThe University of Poonch Rawalakot, Hajira RoadRawalakotPakistan
  3. 3.Neurobiology of Emotions (NAP-USP-NuPNE) Research CentreRibeirão Preto School of Medicine of the University of São Paulo (FMRP-USP)São PauloBrazil
  4. 4.Behavioural Neurosciences Institute (INeC)São PauloBrazil
  5. 5.Department of Neuroscience and Behavioural Sciences, Division of PsychiatryRibeirão Preto Medical School of the University of São Paulo (FMRP-USP)São PauloBrazil
  6. 6.Laboratory of Neurophysiology, Department of PhysiologyRibeirão Preto Medical School of the University of São PauloSão PauloBrazil

Personalised recommendations