1. Involvement of PPAR receptors in the anticonvulsant effects of a cannabinoid agonist, WIN 55,212-2
- Author
-
Ramtin Gholizadeh, Hossein Aghaei, Kazem Mousavizadeh, Ali Ebrahimi, Ahmad Reza Dehpour, Bardia Varastehmoradi, Reza Rahimian, Borna Payandemehr, and Maziar Gooshe
- Subjects
Male ,Agonist ,Cannabinoid receptor ,medicine.drug_class ,Morpholines ,medicine.medical_treatment ,Peroxisome Proliferator-Activated Receptors ,Naphthalenes ,Pharmacology ,Mice ,Piperidines ,Receptor, Cannabinoid, CB1 ,Seizures ,medicine ,Animals ,Anilides ,Drug Interactions ,Receptor ,WIN 55,212-2 ,Cannabinoid Receptor Antagonists ,Oxazoles ,Biological Psychiatry ,Dose-Response Relationship, Drug ,Pioglitazone ,Seizure threshold ,Chemistry ,Antagonist ,Benzoxazines ,Disease Models, Animal ,Anticonvulsant ,Pentylenetetrazole ,Pyrazoles ,Tyrosine ,Anticonvulsants ,Thiazolidinediones ,lipids (amino acids, peptides, and proteins) ,Cannabinoid ,psychological phenomena and processes ,medicine.drug - 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.
- Published
- 2015
- Full Text
- View/download PDF