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WAG/Rij rats show a reduced expression of CB 1 receptors in thalamic nuclei and respond to the CB 1 receptor agonist, R (+)WIN55,212‐2, with a reduced incidence of spike‐wave discharges
Author(s) -
Van Rijn Clementina M.,
Gaetani Silvana,
Santolini Ines,
Badura Aleksandra,
Gabova Aleksandra,
Fu Jin,
Watanabe Masashiko,
Cuomo Vincenzo,
Van Luijtelaar Gilles,
Nicoletti Ferdinando,
Ngomba Richard T.
Publication year - 2010
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2009.02510.x
Subject(s) - am251 , agonist , medicine , endocrinology , receptor , inverse agonist , cannabinoid receptor , chemistry , cannabinoid , receptor antagonist , pharmacology , antagonist , biology
Summary Purpose: Genetically epileptic WAG/Rij rats develop spontaneous absence‐like seizures after 3 months of age. We used WAG/Rij rats to examine whether absence seizures are associated with changes in the expression of type‐1 cannabinoid (CB 1 ) receptors. Methods: Receptor expression was examined by in situ hybridization and western blot analysis in various brain regions of “presymptomatic” 2‐month old and “symptomatic” 8‐month‐old WAG/Rij rats relative to age‐matched nonepileptic control rats. Furthermore, we examined whether pharmacologic activation of CB 1 receptor affects absence seizures. We recorded spontaneous spike‐wave discharges (SWDs) in 8‐month old WAG/Rij rats systemically injected with the potent CB 1 receptor agonist, R (+)WIN55,212‐2 (3–12 mg/kg, s.c.), given alone or combined with the CB 1 receptor antagonist/inverse agonist, AM251 (12 mg/kg, s.c.). Results: Data showed a reduction of CB 1 receptor mRNA and protein levels in the reticular thalamic nucleus, and a reduction in CB 1 receptor protein levels in ventral basal thalamic nuclei of 8‐month‐old WAG/Rij rats, as compared with age‐matched ACI control rats. In vivo, R (+)WIN55,212‐2 caused a dose‐dependent reduction in the frequency of SWDs in the first 3 h after the injection. This was followed by a late increase in the mean SWD duration, which suggests a biphasic modulation of SWDs by CB 1 receptor agonists. Both effects were reversed or attenuated when R (+)WIN55,212‐2 was combined with AM251. Discussion: These data indicate that the development of absence seizures is associated with plastic modifications of CB 1 receptors within the thalamic‐cortical‐thalamic network, and raise the interesting possibility that CB 1 receptors are targeted by novel antiabsence drugs.