INTERACTION OF ANTINOCICEPTIVE EFFECTS OF MORPHINE AND GABA AGONISTS AT THE LEVEL OF SPINAL CORD IN RATS

Abstract

S454 Pharmacological and neurophysical data suggest an antinociceptive interaction between GABA and opioid receptors. This is supported by the potentiation of GABA-induced current by opioid [1], the enhancement of opioid antinociception by benzodiazepines [2], which mainly act on GABAA receptor, and the spinal antinociception of GABA agonists. In contrast, intracerebroventricular injection of GABAA agonist inhibits the morphine antinociceptive effect [3]. However, there have been little information regarding their interaction in the spinal cord. In the present study, we have examined the effects of GABAA agonist, muscimol and GABAB agonist, baclofen on the both of somatic and visceral antinociceptive effects of morphine at the level of spinal cord. METHODS: Following Animal Care approval, an intrathecal catheter was implanted from L4/L5 level in male Sprague Dawley rats. Tail flick (TF) test and colorectal distension (CD) test were employed to measure response to somatic stimulus and visceral stimulus, respectively. In the CD test, the pressure at which abdominal contractions were triggered was defined as the threshold when pressure within the intracolonic balloon was steadily increased. Measurements were performed before and 5, 10, 15, 20, 30, 60, 90, 120 and 180 min after intrathecal administration of morphine, muscimol, baclofen, the combination of those (morphine 1 or 0.1 [micro sign]g and muscimol 0.2 [micro sign]g or baclofen 0.03 [micro sign]g) or saline. Percent of maximum possible effect (%MPE) was calculated by transforming response threshold in TF and CD tests. RESULTS: Intrathecally administered morphine, muscimol or baclofen produced the both somatic and visceral antinociception in a dose dependent fashion. Morphine 1 [micro sign]g increased mean %MPE for 90 min (with a peak effect of 96%MPE at 20 min) in TF test and for 30 min (with a peak effect of 53%MPE at 20 min) in CD test. The combination of 1 [micro sign]g morphine and an ineffective or slightly effective dose of muscimol (0.2 [micro sign]g) or baclofen (0.03 [micro sign]g) produced significant increases in %MPEs compared with morphine 1 [micro sign]g in both tests. Morphine 0.1 [micro sign]g showed slightly increased %MPE in TF test but not in CD test. It was potentiated by GABA agonists in TF test but not in CD test. CONCLUSIONS: The results demonstrate that GABAA, GABAB agonist may potentiate the both somatic and visceral antinociceptive effects of opioid at the level of spinal cord.