NEUROSCIENCE LETTERS | 卷:186 |
KAPPA-OPIOID RECEPTOR AGONISTS SUPPRESS ABSENCE SEIZURES IN WAG/RIJ RATS | |
Article | |
PRZEWLOCKA, B ; LASON, W ; MACHELSKA, H ; VANLUIJTELAAR, G ; COENEN, A ; PRZEWLOCKI, R | |
关键词: ABSENCE EPILEPSY; WAG/RIJ RATS; U50,488H; U69,593, PD117,302; D-ALA(2)-N-METHYL-PHE(4)-GLY(5)-OL-ENKEPHALIN; | |
DOI : 10.1016/0304-3940(95)11303-E | |
来源: Elsevier | |
【 摘 要 】
Involvement of the kappa opioid receptor in the regulation of epileptic activity was studied in WAG/Rij rats, a genetic model of absence epilepsy, I.c.v. administration of the kappa agonists U50,488H {trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidynyl)-cyclohexyl]-benzeneacetamide}, U69,593 (5 alpha,7 alpha,8 beta)-(-)-N-methyl-(1-pyrrolidinyl)-1-oxaspiro(4,5)dec-8-yl)benzeneacetamide) or PD117,302 ((+/-)-trans-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzo[b]thiophene-4-acetamide), 50 and 150 mu g/5 mu l each, dose-dependently decreased the number and mean duration of spike wave discharges (SWD). Peripheral administration of U50,488H (10 and 30 mg/kg s.c.) also attenuated the seizure activity in this model. The specific kappa opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 10 mu g/5 mu l i.c.v., 18 h before EEG registration) moderately increased the number of SWD, which suggests that endogenous opioids acting through a receptors may tonically inhibit the seizure activity in these rats. In addition, the enhancement of an absence-like seizure activity induced by the specific mu opioid receptor agonist D-Ala(2)-N-methyl-Phe(4)-Gly(5)-ol-enkephalin (DAMGO, 0.7 mu g/5 mu l i.c.v.) was also attenuated in rats pretreated with U50,488H, U69,593 or PD117,302. These data indicate that activation of the kappa opioid receptor exerts an inhibitory effect on absence-like seizure activity in WAG/Rij rats.
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