STIMULATION OF SPINAL DELTA-OPIOID RECEPTORS IN MICE SELECTIVELY ENHANCES THE ATTENUATION OF DELTA-OPIOID RECEPTOR-MEDIATED ANTINOCICEPTIONBY ANTISENSE OLIGODEOXYNUCLEOTIDE

Intrathecal (i.t.) pretreatment of male ICR mice with antisense oligod eoxynucleotide to delta-opioid receptor mRNA once a day for 1-3 days c aused a time-dependent attenuation of i.t. administered [D-Ala(2)]delt orphin II-induced antinociception as measured by the tail-flick test. The attenuation of the antinociception induced by i.t. administered [D -Ala(2)]deltorphin II, a delta-opioid receptor agonist, was enhanced b y i.t. pretreatment for 1 day with [D-Ala(2)]deltorphin II, but not [D -Ala(2),NMePhe(4),Gly(ol)(5)]enkephalin (DAMGO), a mu-opioid receptor agonist, or U50,488H, a kappa-opioid receptor agonist, given together with antisense oligodeoxynucleotide to delta-opioid receptor mRNA. The present results indicate that stimulation of spinal delta-opioid rece ptors by i.t. injection of [D-Ala(2)]deltorphin II selectively causes a loss of delta-opioid receptor-mediated antinociception in mice pretr eated with antisense oligodeoxynucleotide to delta-opioid receptor mRN A.