Selective modulation of morphine antinociception, but not development of tolerance, by δ receptor agonists

Co-administration of δ opioid agonists at doses which do not produce measurable antinociception were demonstrated to produce an increase in the antinociceptive potency of morphine in the mouse tail-flick test. In contrast, co-administration of equi-antinociceptive combinations of a δ agonist plus morphine for three days resulted in the development of less tolerance to morphine antinociceptive actions. The data indicate that while acute antinociceptive effects of opioid μ agonists are modulated by δ agonists, the development of antinociceptive tolerance is not.