Zopiclone potentiates the antinociceptive effect of morphine in rats

The antinociceptive effect of morphine, as determined by the tail-flick test, was dose-dependently increased by the intraperitoneal injection of zopiclone. The benzodiazepine antagonists Ro 15-1788 (flumazepil) and Ro 15-3505, when intraperitoneally injected, significantly antagonized the effect of intraperitoneal injection of zopiclone on morphine antinociception. Intrathecal injection of zopiclone potentiated morphine antinociception, while the intracerebroventricular injection of zopiclone failed to enhance morphine antinociception and the intracerebroventricular injection of flumazepil to antagonize the intraperitoneal-zopiclone-induced increase in morphine antinociception. These results suggest that benzodiazepine sites are specifically involved in the potentiating effect of zopiclone on morphine antinociception. The anatomical locations of the receptors involved seem to be at the spinal level.