Antinociception and σ-1 opioid receptors in the rat spinal cord: Studies with intrathecal 7-benzylidenenaltrexone

As part of a continuing investigation of the role of spinal delta opioid receptors in antinociception, this study characterized the ability of 7- benzylidenenaltrexone (BNTX), a selective delta-1 opioid receptor antagonist, to antagonize the antinociception produced in the rat by intrathecal (i.t.) administration of the respective delta-1 and delta-2 opioid receptor agonists, DPDPE and [D-Ala2, Glu4]deltorphin (DELT), or the mu receptor agonist DAMGO. In the tail flick test, 10-min pretreatment with 1 µg of BNTX, increased the ED50 value of DPDPE from 27.5 µg (42.6 nmol) to 114.8 µg (177.8 nmol), but did not increase the ED50 values of either DELT or DAMGO. Increasing the dose of BNTX to 3 µg did not produce a significantly greater antagonism of the antinociceptive effects of DPDPE and did not antagonize the antinociceptive effects of DAMGO. However, it did enhance the antinociceptive effects of DELT decreasing its ED50 from 5.3 to 0.18 µg in the tail flick test. In the hot plate test, 10 min pretreatment with 1 µg of IBNTX selectively antagonized the antinociceptive effects of DPDPE, but did not antagonize the actions of DAMGO or DELT. Increasing the dose of BNTX to 3µg also did not produce a significantly greater antagonism of the antinociceptive effects of DPDPE in the hot plate test, but did antagonize both the increase in hot plate latency and the modest decrement in motor function produced by 30 µg i.t. of DELT. However, the antagonism of these effects of DELT occurred much later in time than BNTX's antagonism of the antinociceptive effects of DPDPE.