Cross-tolerance studies in the spinal cord of beta-FNA-treated mice provides further evidence for delta opioid receptor subtypes.

In this study we investigated the development of cross-tolerance among intrathecally (i.t.)- administered mu and delta opioid receptor selective peptides in beta-funaltrexamine (beta-FNA)-treated mice. Tolerance to the antinociceptive effect of i.t. administered DPDPE was accomplished by administration of 16 nmol/mouse of DPDPE, i.t. 3 hr before testing in beta-FNA-treated mice (10 mumol/kg, s.c., 24 hr before the experiment). Cross-tolerance developed to the antinociceptive effect of i.t. administered DADLE but not to those of DSLET or DAMGO. DSLET (0.1 nmol/mouse i.t.) administration in beta-FNA-treated mice resulted in tolerance development to its antinociceptive effect. The same pretreatment resulted in a marginally significant increase in the antinociceptive ED50 value of DPDPE. There was no cross-tolerance to the antinociceptive effect of i.t. administered DADLE or DAMGO. These results provide further evidence for the existence of delta opioid receptor subtypes where DADLE and DPDPE interact with one site and DSLET with a different one.