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The Role of the Possible Receptors and Intracellular Pathways in Protective Effect of Exogenous Anandamide in Kindling Model of Epilepsy

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Abstract

In this research, the involvement of CB1 and TRPV1 receptors in the possible protective effects of anandamide were investigated in the kindling model of epilepsy. The basolateral amygdala of the rat brain was chosen to put stimulating electrodes. Semi-rapid kindling was induced by a repetitive sub-threshold stimulation for 5–9 consecutive days. There were seven groups, six of which were kindled and used for drug testing by intracerebroventricular (i.c.v.) microinjection. (i) Sham, (ii) control group received vehicles, (iii) anandamide (AEA; 100 ng/rat), (iv) capsazepine (TRPV1 antagonist; 100 ng/rat), (v) AM251 (CB1 antagonist; 100 ng/rat), (vi) AM251 + anandamide, and (vii) capsazepine + anandamide. The after-discharge duration, seizure duration, and stage five duration were measured in rats. Moreover, the expressions of the extracellular signal-regulated kinase (ERK) and the cAMP responsive element binding (CREB) proteins in the hippocampus were also studied. The anandamide-treated group showed a significant decrease in seizure scores, while no change was shown in seizure scores in the capsazepine- and AM251-treated groups compared with the control group. Co-administrations of either capsazepine + AEA or AM251 + AEA attenuated the protective effect of AEA against seizure. Furthermore, the group received AEA showed a decrease in the expressions of CREB and p-CREB possibly through the activation of the CB1 and TRPV1 receptors. Activation of CB1 and TRPV1 receptors might be involved in AEA anticonvulsant effect in kindling model of epilepsy. This effect could be due to suppression of CREB phosphorylation in hippocampal neurons.

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Abbreviations

AEA:

Anandamide

TRPV1:

Transient receptor potential vanilloid type 1

AM251:

1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide

ADD:

After-discharge duration

SD:

Seizure duration

S5D:

Stage five duration

ERK:

Extracellular signal-regulated kinase

CREB:

CAMP responsive element binding

DMSO:

Dimethyl-sulfoxide

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Acknowledgements

The authors thank Dr. Leila Ahmad-Molaei for her technical assistance. The study was supported by Neuroscience Research Center, Shahid Beheshti University of Medical Sciences.

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Authors and Affiliations

  1. Department of Plant Sciences, Biological Sciences, Alzahra University, Tehran, Iran

    Sepideh Khaksar

  2. Department of Physiology and Pharmacology, Pasteur Institute of Iran, Tehran, Iran

    Mona Salimi

  3. Department of Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, No. 2660, Vali-e-Asr Ave, 1996835113, Tehran, Iran

    Hadi Zeinoddini & Nima Naderi

  4. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nima Naderi

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  1. Sepideh Khaksar
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Contributions

Conceived and designed the experiments: NN, MS. Performed the experiments: SK, HZ. Analyzed the data: NN, SK. Wrote the paper: SK, NN.

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Correspondence to Nima Naderi.

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Khaksar, S., Salimi, M., Zeinoddini, H. et al. The Role of the Possible Receptors and Intracellular Pathways in Protective Effect of Exogenous Anandamide in Kindling Model of Epilepsy. Neurochem Res 47, 1226–1242 (2022). https://doi.org/10.1007/s11064-021-03517-5

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