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Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2.

Abstract

Cannabinoid and PPAR receptors show well established interactions in a set of physiological effects. Regarding the seizure-modulating properties of both classes of receptors, the present study aimed to evaluate the roles of the PPAR-gamma, PPAR-alpha and CB1 receptors on the anticonvulsant effects of WIN 55,212-2 (WIN, a non selective cannabinoid agonist). The clonic seizure thresholds after intravenous administration of pentylenetetrazole (PTZ) were assessed in mice weighing 23-30 g. WIN increased the seizure threshold dose dependently. Pretreatment with pioglitazone, as a PPARγ agonist, potentiated the anticonvulsant effects of WIN, while PPARγ antagonist inhibited these anticonvulsant effects partially. On the other hand PPARα antagonist reduced the anticonvulsant effects of WIN significantly. Finally the combination of CB1 antagonist and PPARα antagonist could completely block the anticonvulsant properties of WIN. Taken together, these results show for the first time that a functional interaction exists between cannabinoid and PPAR receptors in the modulation of seizure susceptibility.

Authors+Show Affiliations

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: rahimian78@gmail.com.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Physiology Research Center and Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: mousavik@gmail.com.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25448777

Citation

Payandemehr, Borna, et al. "Involvement of PPAR Receptors in the Anticonvulsant Effects of a Cannabinoid Agonist, WIN 55,212-2." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 57, 2015, pp. 140-5.
Payandemehr B, Ebrahimi A, Gholizadeh R, et al. Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2. Prog Neuropsychopharmacol Biol Psychiatry. 2015;57:140-5.
Payandemehr, B., Ebrahimi, A., Gholizadeh, R., Rahimian, R., Varastehmoradi, B., Gooshe, M., ... Dehpour, A. R. (2015). Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2. Progress in Neuro-psychopharmacology & Biological Psychiatry, 57, pp. 140-5. doi:10.1016/j.pnpbp.2014.11.005.
Payandemehr B, et al. Involvement of PPAR Receptors in the Anticonvulsant Effects of a Cannabinoid Agonist, WIN 55,212-2. Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3;57:140-5. PubMed PMID: 25448777.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2. AU - Payandemehr,Borna, AU - Ebrahimi,Ali, AU - Gholizadeh,Ramtin, AU - Rahimian,Reza, AU - Varastehmoradi,Bardia, AU - Gooshe,Maziar, AU - Aghaei,Hossein Nayeb, AU - Mousavizadeh,Kazem, AU - Dehpour,Ahmad Reza, Y1 - 2014/11/13/ PY - 2014/08/06/received PY - 2014/10/22/revised PY - 2014/11/07/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/8/14/medline KW - Cannabinoid KW - PPAR-alpha KW - PPAR-gamma KW - Seizure KW - WIN 55,212-2 mesylate SP - 140 EP - 5 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 57 N2 - Cannabinoid and PPAR receptors show well established interactions in a set of physiological effects. Regarding the seizure-modulating properties of both classes of receptors, the present study aimed to evaluate the roles of the PPAR-gamma, PPAR-alpha and CB1 receptors on the anticonvulsant effects of WIN 55,212-2 (WIN, a non selective cannabinoid agonist). The clonic seizure thresholds after intravenous administration of pentylenetetrazole (PTZ) were assessed in mice weighing 23-30 g. WIN increased the seizure threshold dose dependently. Pretreatment with pioglitazone, as a PPARγ agonist, potentiated the anticonvulsant effects of WIN, while PPARγ antagonist inhibited these anticonvulsant effects partially. On the other hand PPARα antagonist reduced the anticonvulsant effects of WIN significantly. Finally the combination of CB1 antagonist and PPARα antagonist could completely block the anticonvulsant properties of WIN. Taken together, these results show for the first time that a functional interaction exists between cannabinoid and PPAR receptors in the modulation of seizure susceptibility. SN - 1878-4216 UR - https://www.unboundmedicine.com/medline/citation/25448777/Involvement_of_PPAR_receptors_in_the_anticonvulsant_effects_of_a_cannabinoid_agonist_WIN_55212_2_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(14)00221-8 DB - PRIME DP - Unbound Medicine ER -