title: Differential modulation by muscimol and baclofen on antinociception induced by morphine, beta-endorphin, D-Pen2,5-enkephalin and U50,488H administered intracerebroventricularly in the mouse.
abstract: The present study was designed to investigate the modulatory effects of stimulation of GABAA and GABAB receptors at supraspinal sites on antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. The effects of the GABAA and GABAB receptor agonists, muscimol and baclofen respectively, on the antinociception induced by morphine (a mu-receptor agonist), beta-endorphin (an epsilon-receptor agonist), D-Pen2,5-enkephalin (DPDPE, a delta-receptor agonist) and U50,488H ([trans-3,4-dichloroN-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide]; a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick and hot-plate tests. Muscimol at doses of 25-200 ng, administered i.c.v. alone did not affect the latencies of tail-flick and hot-plate thresholds, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by i.c.v. administered morphine (2 micrograms), beta-endorphin (1 microgram), DPDPE (10 micrograms), and U50,488H (60 micrograms). Baclofen (1.25-10 ng) administered i.c.v. alone did not affect the latencies of the tail-flick and hot-plate responses, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by beta-endorphin and U50,488H, without affecting morphine- or DPDPE-induced responses. Our results indicate that activation of GABAA receptors at the supraspinal sites by i.c.v. injection of muscimol antagonizes antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. On the other hand, activation of GABAB receptors at supraspinal sites by i.c.v. baclofen antagonizes antinociception induced by i.c.v. administered epsilon- and kappa-opioid agonists, but not mu- or delta-opioid agonists.
authors.affiliation: Department of Pharmacology, Hallym University, Kangwon-Do, S. Korea.
authors.forename: H W
authors.initials: HW
authors.lastname: Suh
authors.forename: D K
authors.initials: DK
authors.lastname: Song
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Choi
authors.forename: J S
authors.initials: JS
authors.lastname: Yoo
authors.forename: L F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D018079:Receptors, GABA / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000700:Analgesics; D004745:Enkephalins; D011759:Pyrrolidines; D018079:Receptors, GABA; D017473:Receptors, Opioid, kappa; D009118:Muscimol; D001615:beta-Endorphin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D001418:Baclofen