Skip to main content
SpringerLink
Log in

Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy

  • Original research article
  • Published:
Pharmacological Reports Aims and scope Submit manuscript

Abstract

Background

Modulation of the endocannabinoid (eCB) transmission is a promising approach to treating epilepsy. Animal models can be used to investigate this approach. Krushinsky-Molodkina (KM) rats have, genetically, audiogenic epilepsy. Moreover, in these animals, repeated induction of audiogenic seizures results in a progressive prolongation of the seizures, known as audiogenic kindling.

Methods

The present study evaluated, in these KM rats, acute and long-term effects of a single dose of 4 mg/kg of the cannabinoid-receptor agonist WIN55,212-2.

Results

Administration of the single dose of WIN55,212-2 one hour before the 4th seizure delayed the kindling process by two weeks, without any acute effect on the audiogenic seizures.

Conclusions

This result suggests that short-term potentiation of the eCB system might modify the epileptogenic disease process in patients with a progressive course of epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hofmann ME, Frazier CJ. Marijuana endocannabinoids, and epilepsy: potential and challenges for improved therapeutic intervention. Exp Neurol 2013;244:43–50.

    Article  CAS  PubMed  Google Scholar 

  2. Alger BE. Endocannabinoids at the synapse a decade after the dies mirabilis (29 March 2001): what we still do not know. J Physiol 2012;590(Pt 10): 2203–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Katona I, Freund TF. Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 2012;35:529–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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(1):129–37.

    Article  CAS  PubMed  Google Scholar 

  5. Chen K, Neu A, Howard AL, Foldy C, Echegoyen J, Hilgenberg L, et al. Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures. J Neurosci 2007;27(1):46–58.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Echegoyen J, Armstrong C, Morgan RJ, Soltesz I. Single application of a CB1 receptor antagonist rapidly following head injury prevents long-term hyperexcitability in a rat model. Epilepsy Res 2009;85(1):123–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mechoulam R, Lichtman AH. Neuroscience. Stout guards of the central nervous system. Science 2003;302(5642):65–7.

    CAS  PubMed  Google Scholar 

  8. van Rijn CM, Perescis MF, Vinogradova L, van Luijtelaar G. Endocannabinoid system protects against cryptogenic seizures. Pharmacol Rep 2011;63(1):165–8.

    Article  PubMed  Google Scholar 

  9. Wendt H, Soerensen J, Wotjak CT, Potschka H. Targeting the endocannabinoid system in the amygdala kindling model of temporal lobe epilepsy in mice. Epilepsia 2011;52(7):e62–5.

    Article  PubMed  Google Scholar 

  10. Romanova LG, Zorina ZA, Korochkin LI. A genetic, physiological, and biochemical investigation of audiogenic seizures in rats. Behav Genet 1993;23(5):483–9.

    Article  CAS  PubMed  Google Scholar 

  11. Faingold CL. Emergent properties of CNS neuronal networks as targets for pharmacology: application to anticonvulsant drug action. Prog Neurobiol 2004;72(1):55–85.

    Article  CAS  PubMed  Google Scholar 

  12. Vinogradova LV, van Rijn CM. Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model. Epilepsia 2008;49(7):1160–8.

    Article  CAS  PubMed  Google Scholar 

  13. Jobe PC, Picchioni AL, Chin L. Role of brain norepinephrine in audiogenic seizure in the rat. J Pharmacol Exp Ther 1973;184(1):1–10.

    CAS  PubMed  Google Scholar 

  14. Hirsch E, Danober L, Simler S, Pereira de Vasconcelos A, Maton B, Nehlig A, et al. The amygdala is critical for seizure propagation from brainstem to forebrain. Neuroscience 1997;77(4):975–84.

    Article  CAS  PubMed  Google Scholar 

  15. Tupal S, Faingold CL. Precipitous induction of audiogenic kindling by activation of adenylyl cyclase in the amygdala. Epilepsia 2010;51(3):354–61.

    Article  CAS  PubMed  Google Scholar 

  16. Vinogradova LV, Shatskova AB, van Rijn CM. Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model of audiogenic epilepsy. Epilepsy Res 2011;96(3):250–6.

    Article  CAS  PubMed  Google Scholar 

  17. Ramikie TS, Patel S. Endocannabinoid signaling in the amygdala: anatomy, synaptic signaling, behavior, and adaptations to stress. Neuroscience 2012;204:38–52 [Review].

    Article  CAS  PubMed  Google Scholar 

  18. Tsou K, Brown S, Sanudo-Pena MC, Mackie K, Walker JM. Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system. Neuroscience 1998;83(2):393–411.

    Article  CAS  PubMed  Google Scholar 

  19. Gaffuri AL, Ladarre D, Lenkei Z. Type-1 cannabinoid receptor signaling in neuronal development. Pharmacology 2012;90(1–2):19–39 [Review].

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia

    Lyudmila V. Vinogradova

  2. Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, The Netherlands

    Clementina M. van Rijn

Authors
  1. Lyudmila V. Vinogradova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clementina M. van Rijn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clementina M. van Rijn.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vinogradova, L.V., van Rijn, C.M. Long-term disease-modifying effect of the endocannabinoid agonist WIN55,212-2 in a rat model of audiogenic epilepsy. Pharmacol. Rep 67, 501–503 (2015). https://doi.org/10.1016/j.pharep.2014.12.002

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.pharep.2014.12.002

Keywords

Search

Navigation