Effects of GABA receptor antagonists injected spinally on antinociception induced by opioids administered supraspinally in mice.

The present study was designed to investigate the modulatory effects of blockade of spinal GABAA and GABAB receptors on antinociception induced by supraspinally administered mu- and epsilon-opioid receptor agonists. The effects of intrathecal (i.t.) injections with GABAA and GABAB receptor antagonists, SR 95531 [2-(3-carboxypropyl)-3-amino-6-(4-mehylphenyl)pyridazinium bromide] and 5-aminovaleric acid, respectively, on the antinociception induced by morphine (a mu-opioid receptor agonist) and beta-endorphin (an epsilon-opioid receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. Antinociception was assayed using the tail-flick test. The i.t. injection of SR 95531 (0.04-0.16 nmol) and 5-aminovaleric acid (32.5-130 nmol), administered alone did not affect the latencies of the tail-flick response, but selectively antagonized the inhibition of the tail-flick response induced by muscimol (a GABAA receptor agonist) and baclofen (a GABAB receptor agonist), respectively. The i.t. injection of SR 95531 attenuated dose-dependently the inhibition of the tail-flick response induced by i.c.v. administered morphine, without affecting the i.c.v. administered beta-endorphin-induced response. 5-Aminovaleric acid attenuated dose-dependently the inhibition of the tail-flick response induced by beta-endorphin, without affecting the response to i.c.v. administered morphine. Our results indicate that GABAA but not GABAB receptors located at the spinal cord appears to be involved in the antinociception induced by morphine administered supraspinally whereas GABAB but not GABAA receptors located at the spinal cord may be involved in the antinociception induced by supraspinally administered beta-endorphin, supporting further the hypothesis that morphine and beta-endorphin administered supraspinally produce their antinociception via the activation of different descending pain inhibitory systems.