Effects of chronic administration of 7-benzylidene-7-dehydronaltrexone and naltriben on the antinociceptive actions of delta(1)- and delta(2)-opioid receptor agonists

The effects of chronic administration of 7-benzylidene-7-dehydronaltrexone, a delta(1)-opioid receptor antagonist acid naltriben, a delta(2)-opioid receptor antagonist, on the antinociceptive responses to [D-Pen(2), D-Pen(5)]enkephalin and [D-Ala(2), Glu(4)]deltorphin II, delta(1)- and delta(2)-opioid receptor agonists, respectively, were determined in the mouse. Female B6C3F1 mice were given 7-benzylidene-7-dehydronaltrexone (3 mg/kg/day), naltriben (1 mg/kg/day) or the vehicle by subcutaneously implanted Alzet osmotic minipumps for 7 days. Both [D-Pen(2), D-Pen(5)]enkephalin and [D-Ala(2), Glu(4)]deltorphin II administered intracerebroventricularly (i.c.v.) produced antinociceptive as measured by the tail-flick test with ED(50) values of 6.76 and 6.68 mu g/mouse, respectively. Chronic administration of 7-benzylidene-7-dehydronaltrexone lowered the ED(50) of [D-Pen(2), D-Pen(5)]enkephalin but not of [D-Ala(2), Glu(4)]deltorphin II. Chronic administration of naltriben lowered the ED(50) of [D-Ala(2), Glu(4)]deltorphin II but had no effect on the ED(50) of [D-Pen(2), D-Pen(5)]enkephalin. The binding of [H-3][D-Pen(2), D-Pen(5)]enkephalin to whole brain membranes of chronic 7-benzylidene-7-dehydronaltrexone-treated mice did not differ from chronic vehicle-treated mice. On the other hand, chronic administration of naltriben resulted in slight but reproducible elevation in the B-max value of [H-3][D-Pen(2), D-Pen(5)]enkephalin to bind to whole brain membranes in comparison to vehicle-injected controls. The results suggest that chronic treatment with delta(1)- and delta(2)-opioid receptor antagonist cause behavioral supersensitivity to their agonists, respectively, and provides further evidence for the existence of delta-opioid receptor subtypes.