SPINAL DELTA-OPIOID RECEPTOR SUBTYPE ACTIVITY OF 6-MONOACETYLMORPHINEIN SWISS WEBSTER MICE

Heroin and 6-monoacetylmorphine (6MAM) given intracerebroventricularly in Swiss Webster mice, act on supraspinal delta (delta) opioid recept ors to produce antinociception in the tail flick test. More specifical ly, this action of heroin involves delta(1) and 6MAM involves delta(2) opioid receptors. Even though 6MAM given intrathecally (IT) in Swiss Webster mice also activates delta receptors to produce antinociception , the subtype of delta receptor in the spinal cord is not known. The p resent study addressed this question. First, in order to confirm the s ubtype selectivity of the delta opioid receptor antagonists in the spi nal cord, 7-benzylidenenaltrexone (BNTX a selective delta(1) receptor antagonist) and naltriben (a selective delta(2) receptor antagonist) w ere administered IT against the prototypic delta(1) and delta(2) pepti de agonists [D-Pen(2,5)]enkephalin (DPDPE) and [D-Ser(2),Leu(5)]enkeph alin-Thr (DSLET), respectively. DPDPE-induced antinociception was inhi bited by BNTX, but not naltriben. The opposite selectivity occurred fo r DSLET; naltriben, but not BNTX, administered IT inhibited IT DSLET-i nduced antinociception. Therefore, the antagonists differentiated betw een spinal delta(1) and delta(2) opioid receptor subtype agonist actio ns. This differentiation was further demonstrated by administration of the antagonists IT against the antinociceptive action of beta-endorph in given intracerebroventricularly. The antinociceptive action of beta -endorphin is due to spinal release of met-enkephalin which results in spinal delta(2) receptor activation. This antinociception was reduced by IT naltriben, but not BNTX, administration. The antagonists were t hen administered against IT 6MAM-induced antinociception. Neither BNTX nor naltriben given alone, each at twice the usual dose, altered IT 6 MAM-induced antinociception. When the antagonists were administered to gether, each at the usual dose, the antinociceptive action of 6MAM was inhibited. Thus, even though a differentiation between spinal delta(1 ) and delta(2) opioid receptor activity can be obtained with naltriben and BNTX, blockade of the individual delta receptor subtypes does not appear to alter IT 6MAM antinociception. Therefore, these results sug gest that 6MAM, given IT, is acting on a delta opioid receptor but thi s receptor in the spinal cord appears to be different from the delta(2 ) receptor on which 6MAM acts in the brain. Copyright (C) 1997 Elsevie r Science Inc.