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 μ-, ɛ-, δ-, and κ-opioid receptor agonists. The effects of the GABAA and GABAB receptor agonists, muscimol and baclofen respectively, on the antinociception induced by morphine (a μ-receptor agonist), β-endorphin (an ɛ-receptor agonist), D-Pen2,5-enkephalin (DPDPE, a δ-receptor agonist) and U50,488H ({trans-3,4-di-chloroN-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide}; a κ-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The anti-nociception 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 μg), β-endorphin (1 μg), DPDPE (10 μg), and U50,488H (60 μg). 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 β-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 μ-, ɛ-, δ-, and κ-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 ɛ- and κ-opioid agonists, but not μ- or δ-opioid agonists.
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Suh, H.W., Song, D.K., Kim, Y.H. et al. Differential modulation by muscimol and baclofen on antinociception induced by morphine, β-endorphin, d-Pen2,5-enkephalin and U50,488H administered intracerebroventricularly in the mouse. Naunyn-Schmiedeberg's Arch Pharmacol 352, 614–619 (1995). https://doi.org/10.1007/BF00171319
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DOI: https://doi.org/10.1007/BF00171319