Kappa opioid receptor agonists suppress absence seizures in WAG/Rij rats

Kappa opioid receptor agonists suppress absence seizures in WAG/Rij rats Involvement of the κ 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 κ agonists U50,488H { trans -3,4-dichloro- N -methyl- N -(2-(1-pyrrolidynyl)-cyclohexyl)-benzeneacetamide}, U69,593 (5α,7α,8β)-(−)- 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 μg/5 μl each, dose-dependently decreased t 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 κ opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 10 μg/5 μl i.c.v., 18 h before EEG registration) moderately increased the number of SWD, which suggests that endogenous opiods acting through κ receptors may tonically inhibit the seizure activity in these rats. In addition, the enhancement of an absence-like seizure activity induced by the specific μ opioid receptor agonist d -Ala 2 - N -methyl-Phe 4 -Gly 5 -ol-enkephalin (DAMGO, 0.7 μg/5 μl i.c.v.) was also attenuated in rats pretreated with U50,488H, U69,593 or PD117,302. These data indicate that activation of the κ opioid receptor exerts an inhibitory effect on absence-like seizure activity in WAG/Rij rats. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuroscience Letters Elsevier

Kappa opioid receptor agonists suppress absence seizures in WAG/Rij rats

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Ltd
ISSN
0304-3940
DOI
10.1016/0304-3940(95)11303-E
Publisher site
See Article on Publisher Site

Abstract

Involvement of the κ 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 κ agonists U50,488H { trans -3,4-dichloro- N -methyl- N -(2-(1-pyrrolidynyl)-cyclohexyl)-benzeneacetamide}, U69,593 (5α,7α,8β)-(−)- 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 μg/5 μl each, dose-dependently decreased t 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 κ opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 10 μg/5 μl i.c.v., 18 h before EEG registration) moderately increased the number of SWD, which suggests that endogenous opiods acting through κ receptors may tonically inhibit the seizure activity in these rats. In addition, the enhancement of an absence-like seizure activity induced by the specific μ opioid receptor agonist d -Ala 2 - N -methyl-Phe 4 -Gly 5 -ol-enkephalin (DAMGO, 0.7 μg/5 μl i.c.v.) was also attenuated in rats pretreated with U50,488H, U69,593 or PD117,302. These data indicate that activation of the κ opioid receptor exerts an inhibitory effect on absence-like seizure activity in WAG/Rij rats.

Journal

Neuroscience LettersElsevier

Published: Feb 17, 1995

References

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