Effect of Cannabinoid Receptor Activation on Spreading Depression

Document Type : Original Article

Authors

1 Shefa Neuroscience Research Centre, Tehran, Iran

2 Department of Pediatrics, Shahed University, Tehran, Iran

3 Institut für Physiologie I, Westfalische Wilhelms-Universitat Munster, Münster, Germany

4 Institut für Physiologie I, Westfalische Wilhelms-Universitat Munster, Münster, German

5 Institut für Experimentelle Epilepsieforschung, Westfalische Wilhelms-Universitat Munster, Münster, Germany

Abstract

Objective(s)
The objective of this study was to evaluate the effect of cannabinoid on cortical spreading depression (CSD) in rat brain. Cannabis has been used for centuries for both symptomatic and prophylactic treatment of different types of headaches including migraine. CSD is believed to be a putative neuronal mechanism underlying migraine aura and subsequent pain.
Materials and Methods
The effects of Delta9-tetrahydrocannabinol (THC), as well as, cannabinoid CB1 and CB2 receptor agonists on CSD in rat neocortical slices were investigated. Furthermore, the effect of cannabinoid CB1 agonist was tested on field excitatory postsynaptic potentials (fEPSP) and long-term potentiation (LTP).
Results
HC (1-20 microM) dose dependently suppressed CSD amplitude, duration, and propagation velocity. Cannabinoid CB1 agonist, WIN 55,212-2 mesylate (1-10 microM), also significantly suppressed all characteristic features of CSD. However, cannabinoid CB2 agonist, JWH-133 (1-20 microM), did not affect CSD. FEPSP and induction of LTP were suppressed by application of WIN55212-2.
Conclusion
Suppression of CSD by activation of CB1 receptors points to the potential therapeutic effects of cannabinoids in migraine with aura. More research is needed before we know whether cannabinoids may be helpful in treating migraine pain.

Keywords

References

1. Russo EB. Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Neuro Endocrinol Lett  2004: 25:31-39.
2. Gorji A. Pharmacological treatment of headache using traditional Persian medicine. Trends Pharmacol Sci 2003; 24:331-334.
3. Iversen L. Cannabis and the brain. Brain 2003; 26:1252–1270.
4. Misner DL, Sullivan JM. Mechanism of cannabinoid effects on long-term potentiation and depression in hippocampal CA1 neurons. J Neurosci 1999; 19:6795–6805.
5.  Howlett AC. Efficacy in CB1 receptor-mediated signal transduction. Br J Pharmacol 2004; 142:1209-1218.
6. Greco R, Gasperi V, Maccarrone M, Tassorelli C. The endocannabinoid system and migraine. Exp Neurol  2010; 224:85-91.
7. Maione S, Bisogno T, de Novellis V, Palazzo E, Cristino L, Valenti M, et al. Elevation of endocannabinoid levels in the ventrolateral periaqueductal grey through inhibition of fatty acid amide hydrolase affects descending nociceptive pathways via both cannabinoid receptor type 1 and transient receptor potential vanilloid type-1 receptors. J Pharmacol Exp Ther 2006; 316:969-982.
8. Akerman S, Kaube H, Goadsby PJ. Anandamide is able to inhibit trigeminal neurons using an in vivo model of trigeminovascular-mediated nociception. J Pharmacol Exp Ther 2004; 309:56-63.
9. Akerman S, Holland PR, Goadsby PJ. Cannabinoid (CB1) receptor activation inhibits trigeminovascular neurons. J Pharmacol Exp Ther 2007; 320:64-71.
10. Evans RW, Ramadan NM. Are cannabis-based chemicals helpful in headache? Headache 2004; 44:726-727.
11. Leao AAP. Spreading depression of activity in the cerebral cortex. J. Neurophysiol 1944; 7:359–390.
12. Bures J. Leao's spreading depression of EEG activity. Brain Res Bull  1999; 50:459.
13. Somjen GG. Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev 2001; 81:1065-1096.
14. Sanchez-Del-Rio M, Reuter U, Moskowitz MA. New insights into migraine pathophysiology. Curr Opin Neurol  2006; 19:294-298.
15. Goadsby P. Recent advances in understanding migraine mechanisms, molecules and therapeutics. Trends Mol Med  2007; 13:39-44.
16. Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Schwartz D, Bakker D, Fischl B, et al. Mechanisms of migraine aura revealed by functional MRI in human visual cortex. Proc Natl Acad Sci USA 2001; 98:4687–4692.
17. Moskowitz MA, Nozaki K, Kraig RP. Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J. Neurosci 1993; 13:1167–1177.
18. Bolay H, Reuter U, Dunn AK,Huang Z, Boas DA, Moskowitz MA. Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. Nat Med 2002; 8:136–142.
19. Gorji A, Zahn PK, Pogatzki EM, Speckmann EJ. Spinal and cortical spreading depression enhance spinal cord activity. Neurobiol Dis 2004; 15:70-79.
20. Noseda R, Constandil L, Bourgeais L, Chalus M, Villanueva L. Changes of meningeal excitability mediated by corticotrigeminal networks: a link for the endogenous modulation of migraine pain. J Neurosci 2010; 30:14420-14429.
21. Gorji A, Scheller D, Tegtmeier F, Köhling R, Straub H, Speckmann EJ. NiCl2 and amiloride induce spreading depression in guinea pig hippocampal slices. Cephalalgia 2000; 20:740-747.
22. Khaleghi Ghadiri M, Tutam Y, Wassmann H, Speckmann EJ, Gorji A. Periodic fasting alters neuronal excitability in rat neocortical and hippocampal tissues. Neurobiol Dis 2009 ; 36:384-392.
23.Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science  2005; 310:329-332.
24. Hill EL, Gallopin T, Ferezou I, Cauli B, Rossier J, Schweitzer P, Lambolez B. Functional CB1 receptors are broadly expressed in neocortical GABAergic and glutamatergic neurons. J Neurophysiol  2007; 97:2580-2589.
25. el Manira A, Clarac F. Presynaptic inhibition is mediated by histamine and GABA in the crustacean escape reaction. J Neurophysiol 1994; 71:1088-1095.
26. Hoffman AF, Lupica CR. Mechanisms of cannabinoid inhibition of GABA (A) synaptic transmission in the hippocampus. J Neurosci  2000; 20:2470-2479.
27. Becker K, Eder M, Zieglgansberger W, Dodt HU. WIN 55,212-2 decreases the spatial spread of neocortical excitation in vitro. Neuroreport  2005; 16:993-996.
28. Pistis M, Perra S, Pillolla G, Melis M, Gessa GL, Muntoni AL. Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence for CB1- and non-CB1-mediated actions. Neuropharmacology 2004; 46:115-125.
29. Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther  2003; 307:129–137.
30. Fortin DA, Levine ES. Differential effects of endocannabinoids on glutamatergic and GABAergic inputs to layer 5 pyramidal neurons. Cereb Cortex  2007; 17:163-174.
31. Pontzer NJ, Hosko MJ, Wilkison DM. Alteration of electrical correlates of sensory processing by tetrahydrocannabinol. Exp Neurol  1986; 91:127-135.
32. Wilkison DM, Pontzer N, Hosko MJ. Slowing of cortical somatosensory evoked activity by delta 9-tetrahydrocannabinol and dimethylheptylpyran in alpha-chloralose-anesthetized cats. Neuropharmacology 1982; 21:705-709.
33. Patel S, Gerrits R, Muthian S, Greene AS, Hillard CJ. The CB1 receptor antagonist SR141716 enhances stimulus-induced activation of the primary somatosensory cortex of the rat. Neurosci Lett  2002; 335:95-98.
34. Shen M, Piser TM, Seybold VS, Thayer SA. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures. J Neurosci 1996; 16:4322.
35. Sullivan JM. Mechanisms of cannabinoid-receptor-mediated inhibition of synaptic transmission in cultured hippocampal pyramidal neurons. J Neurophysiol 1999; 82:1286-1294.
36. Hampson AJ, Bornheim LM, Scanziani M, Yost CS, Gray AT, Hansen BM, et al. Dual effects of anandamide on NMDA receptor-mediated responses and neurotransmission. J Neurochem 1998; 70:671-676.
37. Netzeband JG, Conroy SM, Parsons KL, Gruol DL. Cannabinoids enhance NMDA-elicited Ca2+ signals in cerebellar granule neurons in culture. J Neurosci 1999; 19:8765-8777.
38. Antonelli T, Tomasini MC, Tattoli M, Cassano T, Tanganelli S, Finetti S, et al. Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and emotional reactivity changes in rat offspring. Cereb Cortex 2005; 15:2013-2020.
39. Kathmann M, Bauer U, Schlicker E, Gothert M. Cannabinoid CB1 receptor-mediated inhibition of NMDA- and kainate-stimulated noradrenaline and dopamine release in the brain. Naunyn Schmiedebergs Arch Pharmacol  1999; 359:466-470.
40. Shen M, Thayer SA. Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol Pharmacol  1998; 54:459-462.
41.Obrenovitch TP. High extracellular glutamate and neuronal death in neurological disorders. Cause, contribution or consequence? Ann N Y Acad Sci  1999; 890:273-286.
42. Gorji A. Spreading depression: a review of the clinical relevance. Brain Res Brain Res Rev  2001; 38:33-60.
43. Gorelova NA, Koroleva VI, Amemori T, Pavlik V, Bures J. Ketamine blockade of cortical spreading depression in rats. Electroencephalogr Clin Neurophysiol  1987; 66:440-447.
44. Sheardown MJ.The triggering of spreading depression in the chicken retina: a pharmacological study. Brain Res 1993; 607:189-194.
45. Peeters M, Gunthorpe MJ, Strijbos PJ, Goldsmith P, Upton N, James MF. Effects of pan- and subtype-selective NMDA receptor antagonists on cortical spreading depression in the rat: therapeutic potential for migraine. J Pharmacol Exp Ther 2007; 321:564-572.
46. Faria LC, Mody I. Protective effect of ifenprodil against spreading depression in the mouse entorhinal cortex. J Neurophysiol  2004; 92:2610-2614.
47. Urenjak J, Obrenovitch TP. Pharmacological investigation into the involvement of nitric oxide in K+-induced cortical spreading depression. Naunyn Schmiedeberg’s Arch Pharmacol 2000; 362:137–144.
48. White HL, Tansik RL. Effects of delta 9-tetrahydrocannabinol and cannabidiol on phospholipase and other enzymes regulating arachidonate metabolism. Prostaglandins Med 1980; 4:409-417.
49. Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A 1999; 96:13496-13500.
50. Collingridge GL, Singer W. Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci  1990; 11:290-296.
51. Davies SN, Pertwee RG, Riedel G. Functions of cannabinoid receptors in the hippocampus. Neuropharmacology 2002; 42:993-1007.
52. Slanina KA, Roberto M, Schweitzer P. Endocannabinoids restrict hippocampal long-term potentiation via CB1. Neuropharmacology  2005; 49:660-668.
53. Auclair N, Otani S, Soubrie P, Crepel F. Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons. J Neurophysiol  2000; 83:3287-3293.
54. Bohme GA, Laville M, Ledent C, Parmentier M, Imperato A. Enhanced long-term potentiation in mice lacking cannabinoid CB1 receptors. Neuroscience 2000; 95:5-7.
55. Footitt DR, Newberry NR. Cortical spreading depression induces an LTP-like effect in rat neocortex in vitro. Brain Res  1998; 781:339-342.
56. Berger M, Speckmann EJ, Pape HC, Gorji A. Spreading depression enhances human neocortical excitability in vitro. Cephalalgia 2008; 28:558-562.
57. Muller M, Pape HC, Speckmann EJ, Gorji A. Effect of eugenol on spreading depression and epileptiform discharges in rat neocortical and hippocampal tissues. Neuroscience 2006; 140:743-751.
58. Dehbandi S, Speckmann EJ, Pape HC, Gorji A. Cortical spreading depression modulates synaptic transmission of the rat lateral amygdala. Eur J Neurosci  2008; 27:2057-2065.
59. Sachs M, Pape HC, Speckmann EJ, Gorji A. The effect of estrogen and progesterone on spreading depression in rat neocortical tissues. Neurobiol Dis  2007; 25:27-34.
60. Wernsmann B, Pape HC, Speckmann EJ, Gorji A. Effect of cortical spreading depression on synaptic transmission of rat hippocampal tissues. Eur J Neurosci 2006; 23:1103-1110.
61. Ghadiri MK, Kozian M, Ghaffarian N, Stummer W, Kazemi H, Speckmann EJ, Gorji A. Sequential changes in neuronal activity in single neocortical neurons after spreading depression. Cephalalgia 2012; 32:116-24.
62. Sadeghian H, Jafarian M, Karimzadeh F, Kafami L, Kazemi H, Coulon P, Ghabaee M, Gorji A. Neuronal death by repetitive cortical spreading depression in juvenile rat brain. Exp Neurol. 2012; 233:438-46.
63. Ebersberger A, Schaible HG, Averbeck B, Richter F. Is there a correlation between spreading depression, neurogenic inflammation, and nociception that might cause migraine headache? Ann Neurol 2001; 49:7-13.

Files

Share

How to cite

Statistics